- Founding of Pennsylvania (January 5). William Penn wrote, "This day my country was confirmed to me by the name of Pennsylvania, a name the King would give it, in honour of my father."
- First brick house erected in this country (Penn's house).
- The first parks or public enclosures laid out in North America for the pleasure and convenience of the people were shown on the plan for Philadelphia (designed by Thomas Holme), in the Northeastern, Southeastern, Northwestern, Southwestern and Centre Squares of the city.
- First almanac printed, "America's Messenger," William Bradford.
- The first paper mill established in North America was built upon the Wissahickon, near Germantown, by William Bradford.
- February 12 The first public school in the America Colonies was established at Philadelphia, and a corporation created, entitled "The Overseers of the Publick Schoole founded in Philadelphia." In this school it was ordered by the governor and Council: "All children and servants, male and female, whose parents, guardians and masters be willing to subject ym to the rules and orders of the said schoole, shall from time to time, with the approbaon of the overseers thereof for the time being, be received or admitted, taught or instructed; the rich at reasonable rates, and the poor to be maintained and schooled for nothing." The first school house was built on the east side of Fourth Street below Chestnut Street. Inoch Flower was the first Schoolmaster.
- The first Presbytery in the United States was organized at Philadelphia by seven Presbyterian ministers.
- The Common Council's resolution, passed this year to the effect that "A work-house Be Immediately Hired to Employ poor P'sons & Sufficient P'sons appointed to keep them at Work," led, in time, to the erection of the Blockley Hospital, the largest of its kind.
- First fire engine bought by any municipality for public purposes.
- December 22 The American Weekly Mercury, the first newspaper established in the Middle Colonies, was issued at Philadelphia by William Bradford.
- John Bartram commenced on the bank of the Schuylkill the first of America's botanical gardens.
- The first botanic garden, for the cultivation of plants having medicinal properties, was established at Bachelor's Hall, Kensington, in the neighborhood of the present Allen and Shackamaxon Streets.
- The first treatise against slavery published in any part of the world appeared at Philadelphia, and was written by Ralph Sandiford.
- The Mariner's Quadrant was invented by Thomas Godfrey of Germantown, and being taken to England, was introduced into use by one Hadley, who unjustly claimed to be the inventor.
- July 31 The Library Company of Philadelphia, the first public institution of that kind in America, was founded in Philadelphia by Benjamin Franklin, Thomas Hopkinson, Thomas Cadwalader and others.
- The Philadelphia Hospital, the oldest in America, was established in connection with the Philadelphia Almshouse.
- American type founding made its debut as an art in the shop of Christopher Sauer, in Germantown, and it was first carried on as a regular business in this city immediately after the War of the Revolution by John Baine.
- December 7th. The Union Fire Company, the first voluntary association for the extinguishment of fires in the United States, and probably in the world, was founded in Philadelphia by Benjamin Franklin and others.
- The American Philosophical Society, the first institution devoted to science in North America, was founded at Philadelphia by Benjamin Franklin, John Bartram, Dr. Thomas Bond, Thomas Godfrey and others.
- The first Bible in a European language printed in North America was published in German by Christopher Sauer of Germantown.
- The first religious magazine established in North America was published in the German language by Christopher Sauer.
- The first company of American stage players was organized here early in 1749.
- First scientific institution in America, founded by Benjamin Franklin.
- February 7 The Pennsylvania Hospital, the first establishment in North America devoted to the relief of the sick and suffering, was chartered by the Assembly of Pennsylvania, at the solicitation of Benjamin Franklin, Dr. Thomas Bond, Rev. Richard Peters and others.
- The Philadelphia Contributionship for insurance against losses by fire was established in Philadelphia, being the first fire insurance company established in the American Colonies.
- June 15 The theory that lightning and electricity were the same, which was first suggested by Benjamin Franklin in 1749, was demonstrated by him by drawing lightning from the clouds by means of a kite. The experiment is said to have taken place upon a lot on the east side of Ridge Road, near the present intersection of Buttonwood Street. Franklin was assisted on the occasion by his son, William Franklin, who was then twenty-one years old.
- September The first lightning-rod used in the world for the protection of a building from danger by lightning was set up by Benjamin Franklin, at his dwelling house, southeast corner of Second and Race Streets.
- Pass & Stowe made for the State House the first bell ever cast in this country.
- March 4 The first expedition fitted out in North America for Arctic exploration and the discovery of a northwest passage, sailed from Philadelphia in the schooner Argo, Captain Charles Swaine. The expedition was fitted out by subscriptions in Philadelphia. The vessel proceeded as far as Cape Farewell and Hudson Straite, but being baffled by the ice, was compelled to return to Philadelphia, which port was reached in November of the same year. The same vessel went upon a second voyage in the spring of 1754, but having lost three men, killed by Native Americans on the Labrador coast, returned in October of the same year without success.
- November 26 The first school of anatomy in North America was opened in Philadelphia by Dr. William Shippen.
- Dr. John Morgan's "Discourse Upon the Institution of Medical Schools in America," delivered in the College of Philadelphia, May 30, 1765, constituted the formal opening of the first medical school, and the speaker filled the first medical professorship created in this country. In consequence whereof a "Commencement" was held three years later (in 1768), at which medical honors were conferred, the first in point of time in America.
- The first permanent theatre house in America was built here in Southwark.
- The first medical society in North America was in existence at Philadelphia.
- The first life insurance society, organized for the relief of widows and orphans of the clergymen of the Church of England, was started here.
- The American Medical Society was founded in this city by students who came from different parts of the Unions to attend the medical lectures here.
- Philadelphia philanthropists formed the first Anti-Slavery Society.
- The physicians of Philadelphia formed the "Society for Inoculating the Poor," the first benevolent association designed to mitigate the horrors of small-pox founded in the Colonies.
- The first pianoforte manufactured in the United States was made by John Behrent, in Third Street below Brown.
- In the war against British importations, started in 1775, William Calverly, of this city, set about making American carpets, a local industry destined in time to fulfill the aim of its founder to such an extent that at the present day Philadelphia manufactures more carpets than the whole of Great Britain.
- First American work on medicine by Dr. Benjamin Rush.
- The Assembly, in session here, passed the first Abolition Act in America.
- The Pennsylvania Bank, the first public bank in the United States, was organized here by Robert Morris.
- May 26 The Bank of North America was established by resolution of Congress, and opened for business in 1783, being the first corporate banking institution established in the United States.
- Robert Aitken, of Philadelphia, brought out the first English Bible in this country.
- The Pennsylvania Packet or General Advertiser was established as a daily newspaper by John Dunlap and David C. Claypoole, being the first daily paper published in the United States.
- The first agriculture society on this continent was "The Philadelphia Society for Promoting Agriculture, " formed by Dr. Rush, Robert Morris, Richard Peters and others in 1785.
- The Philadelphia Dispensary for the medical relief of the poor, the first institution of the kind in the United States, was established by Dr. Benjamin Rush.
- July 20th. The first vessel ever moved by steam was navigated on the Delaware River, at Philadelphia, by John Fitch, being a skiff fitted up for the purpose.
- August 22 A steamboat, forty-five feet long, navigated at Philadelphia, in presence of the delegates to form a Constitution of the United States, by John Fitch, assisted by Henry Voight.
- July Another steamboat, sixty feet long, navigated from Philadelphia to Burlington, New Jersey, By John Fitch.
- The first Congress of the United States met here in Congress Hall.
- December A new steamboat navigated at Philadelphia by John Fitch.
- The Law School of the University of Pennsylvania, the oldest law school in America, was founded in 1790, with James Wilson of the United States Supreme Court, as professor of law.
- Opening of the first Stock Exchange started in America.
- June-September The first steamboat navigated in the world for a passenger and freight-boat ran on the Delaware, between Philadelphia, Burlington, Bristol, Chester, Wilmington, etc., advertising her trips regularly in the newspapers and passing over three thousand miles in that summer. This was seventeen years before the Clermont, Robert Fultons' first steamboat, navigated the Hudson River.
- The Schuylkill and Susquehanna Canal Company, the first public canal company in this country, was chartered here.
- First carpet factory started.
- June 21 The Philadelphia and Lancaster Turnpike Co. chartered, which made and established the first turnpike-road laid in Pennsylvania.
- The Mint of the United States established at Philadelphia, by virtue of act of Congress, being the first Federal mint in the United States.
- The Columbianum, the first society for the promotion of the fine arts, in the United States, was established at Philadelphia by Charles Willson Peale and Joseph Cerrachi, painters, William Rush, sculptor, and others.
- September 22, November 10 The first voyage ever accomplished by a vessel between Lake Erie and Philadelphia was made by the schooner Whitefish, under command of John Thompson and David Lummis. The vessel was eighteen feet keel, twenty-three feet from stem to stern and six feet beam, without a deck. The route was from Presque Isle, now Erie City, by way of Buffalo harbor; thence by the Niagara River to the mouth of the Chippewa; thence by wagon, on which the schooner was placed, by land to Queenstown, where the boat was launched; thence down the Niagara and along Lake Ontario to Great Sodus and Oswego River to the Falls; around the Falls by land carriage one mile; thence by water to the confluence of the Onondaga and Oneida Rivers we go; up the latter through Oneida Lake and Wood's Creek to a portage of one mile between the latter and the Mohawk River, over the same by land carriage; thence down the Mohawk to Little Falls to the same; thence by portage one mile, and down the Mohawk again to Schenectady; then by land carriage to Albany, where the schooner was for the last time launched, thence by the Hudson River, the Narrows along the Jersey coast to Cape May, and up the river Delaware to Philadelphia. The Whitefish after this voyage was taken to Peale's Museum, and for many years remained in the State House yard, until it fell to pieces.
- First American type foundry, Binney & Ronaldson.
- May 2 The Philadelphia Water Works, the first of the kind in the country, were commenced, and the water first sent through the pipes January 21, 1801.
- The Eruktor Amphibolis, a machine for cleaning docks, invented by Oliver Evans, mounted on a wagon, was propelled by steam along Market Street from Centre Square to the Schuylkill River, being the first land carriage ever propelled by steam in the world. At the Schuylkill River the vessel was launched, a stern wheel attached, and the machine was navigated by steam down the Schuylkill and up the Delaware River to the city of Philadelphia.
- First printing ink works, Charles Eneu Johnson.
- The Pennsylvania Academy of the Fine Arts, the pioneer of all art institutions in this country, was founded in 1805, and chartered March 28 of the following year.
- Joseph Hawkins, of Philadelphia, manufactured the first carbonated water made in America.
- The steamboat Phoenix, the first steam vessel which ever navigated the Atlantic Ocean, arrived from Hoboken, New Jersey, where the vessel had been built by John Stevens.
- September The first experimental railroad track laid down in the United States was constructed by Somerville, a Scotch millwright, for Thomas Leiper of Philadelphia, and laid down in a yard adjoining the Bull's Head Tavern, in the Northern Liberties. It was sixty yards in length, and graded an inch and a half to the yard. The gauge was four feet, the sleepers eight feet apart. The experiment with a loaded car was so successful that Leiper had the first practical railroad built in the United States constructed for the transportation of stone from his quarries on Crum Creek to his landing on Ridley Creek, Delaware County, Pennsylvania, a distance of about one mile. It continued in use for nineteen years, and was superseded in 1828 by a canal, which was again superseded in 1852 by a railroad.
- A line of telegraphs (semaphore) was set up and operated by Jonathan Grant, between the head of Delaware Bay to Reedy Island and Philadelphia, under patronage of the Philadelphia Chamber of Commerce.
- The first insurance corporation was organized in this city.
- First Savings Fund Society in America.
- Steam works for supplying the city with water were begun in Fairmount Park; and in 1819 Councils erected water power works for the same purpose, which was and for a long time remained the only works of their kind in the States.
- Joseph Lancaster started the "Model School" of Philadelphia, the first Normal School in the United States.
- The first lithograph executed in America appeared in the June issue of the (Philadelphia) Analectic Magazine.
- The Philadelphia College of Pharmacy dates its birth from 1812.
- First American Manufacturer's exhibit was held in Carpenter's Hall.
- The Pennsylvania Horticultural Society was the first of all such societies in America, having been founded in November, 1827, by a number of Philadelphians under the leadership of Dr. James Meade.
- G. A. Shyrock, of this city, earned the distinction of being the first to make paper and boards by machinery from straw and grass.
- First penny newspaper, The Cent, published by C. C. Conwell.
- First successful women's magazine, Godey's Lady's Book, Louis A. Godey, Sixth Street, above Chestnut.
- Organizing the first building and loan association, January 31, 1831, The Oxford Provident of Frankford.
- Matthias W. Baldwin built an experimental locomotive engine according to his own plans, and differing in many respects from the English engines, which was tested on April 25th on a railroad track laid down in the Philadelphia Museum Arcade, Chestnut Street, and was exhibited there afterward. Subsequently the same engine ran for several months upon a railroad track laid down at Smith's Labyrinth Garden, on the north side of Arch Street, between Schuylkill Seventh and Eighth (Fifteenth and Sixteenth).
- In this year Matthias W. Baldwin founded here what has become the largest locomotive building works in the world.
- First systematic study of meteorology in aid of agriculture, by Franklin Institute.
- First gas pipes in this country were laid here in compliance with an ordinance passed by the two City Chambers.
- First issue of the John-Donkey, the first comic paper to be regularly published.
- The Spring Garden Institute, for the teaching of useful arts to wage-earning youths, the first of its kind in America, was organized.
- For the first time in our history the degree of medicine was conferred upon women at the Female Medical College (now Woman's Medical College) of Philadelphia.
- "The Northern Home," founded in this city in 1853, was the first institution in this broad land when the Civil War broke out to open its doors to the children of those who desired to enlist and too build a special home for the orphans of our dead soldiers and sailors.
- The Consolidation Act of the City and Country of Philadelphia was the first instance of the modern method of making "greater cities."
- Children's Hospital of Philadelphia opened as the first pediatric hospital in the United States.
- The Numismatic and Antiquarian Society, whose ranks have since been joined by the most illustrious men of the two hemispheres, and whose scale of measurement for coins and medals is now in general us throughout Europe, was organized by a few Philadelphians on December 27th.
- Zoological Garden. First in America. A collection of living animal acknowledged to be by far the best in this country.
- Joseph Wharton, of Philadelphia, was the first man in the world to produce pure malleable nickel.
- The first World's Fair in this country was held here to celebrate the Centennial anniversary of the Declaration of Independence.
- The Company was organized which built the present Philadelphia Bourse, the largest in any country and the only one in this.
- Introduction of the pneumatic mailing tube, the first in this country.
- Founding of the Wistar Institute of Anatomy, the first of its kind in America.
- The first Commercial Museum in America was organized in this city.
- National Export Exposition, the first of its nature in the commercial history of the United States.