Francis Hopkinson was born at Philadelphia in 1737, the son of Thomas Hopkinson and Mary Johnson. He became a member of the first class at the College of Philadelphia (now the University of Pennsylvania) in 1751 and graduated in 1757, receiving his master's degree in 1760, and a Doctor in law (honorary) in 1790. He was secretary to a Provincial Council of Pennsylvania Indian commission in 1761 that made a treaty with the Delaware and several Iroquois tribes. In 1763, he was appointed customs collector for Salem, New Jersey. Hopkinson spent from May 1766 to August 1767 in England in hopes of becoming commissioner of customs for North America. Although unsuccessful, he spent time with the Future Prime Minister Lord North, Hopkinson's cousin James Johnson (Bishop of Worcester), and the Painter Benjamin West.

Hopkinson began to play the harpsichord at age seventeen and, during the 1750s, hand-copied arias, songs, and instrumental pieces by many European composers. He is credited as being the first American born Composer to commit a composition to paper with his 1759 composition "My Days Have Been So Wondrous Free." By the 1760s he was good enough on the harpsichord to play with professional Musicians in concerts. Some of his more notable songs include "The Treaty", "The Battle of the Kegs", and "The New Roof, a song for Federal Mechanics". He also played organ at Philadelphia's Christ Church and composed or edited a number of hymns and psalms including: "A Collection of Psalm Tunes with a few Anthems and Hymns Some of them Entirely New, for the Use of the United Churches of Christ Church and St. Peter's Church in Philadelphia" (1763), "A psalm of thanksgiving, Adapted to the Solemnity of Easter: To be performed on Sunday, the 30th of March, 1766, at Christ Church, Philadelphia" (1766), and "The Psalms of David, with the Ten Commandments, Creed, Lord's Prayer, &c. in Metre" (1767). In the 1780s, Hopkinson modified a glass harmonica to be played with a keyboard and invented the Bellarmonic, an instrument that utilized the tones of metal balls.

After his return, Hopkinson operated a dry goods Business in Philadelphia and married Ann Borden on September 1, 1768. They would have five children.

Hopkinson obtained a public appointment as a customs collector for New Castle, Delaware on May 1, 1772. He moved to Bordentown, New Jersey in 1774, became a member of the New Jersey Provincial Council, and was admitted to the New Jersey bar on May 8, 1775. He resigned his crown-appointed positions in 1776 and, on June 22, went on to represent New Jersey in the Second Continental Congress where he signed the Declaration of Independence. He was appointed to Congress’ Marine Committee in that year. He departed the Congress on November 30, 1776 to serve on the Navy Board at Philadelphia. The Board reported to the Marine Committee. Hopkinson later became the Navy Board’s chairman. As part of the nation's government, he was treasurer of the Continental Loan Office in 1778; appointed judge of the Admiralty Court of Pennsylvania in 1779 and reappointed in 1780 and 1787; and helped ratify the Constitution during the constitutional convention in 1787.

Hopkinson wrote popular airs and political satires (jeux d'esprit) in the form of poems and pamphlets. Some were widely circulated, and powerfully assisted in arousing and fostering the spirit of political independence that issued in the American Revolution. His principal writings are A Pretty Story . . . (1774), a satire about King George, The Prophecy (1776), and The Political Catechism (1777).

On Saturday, June 14, 1777, the Second Continental Congress adopted the Stars and Stripes as the first official national flag of the newly independent United States (later celebrated as Flag Day). The resolution creating the flag came from the Continental Marine Committee. Hopkinson became a member of the committee in 1776. At the time of the flag’s adoption, he was the Chairman of the Navy Board, which was under the Marine Committee. Today, that office and responsibility/power would be residing in the United States Secretary of the Navy.

The Treasury Board turned down the request in an October 27, 1780, report to Congress. The Board cited several reasons for its action, including the fact that Hopkinson "was not the only person consulted on those exhibitions of Fancy [that were incidental to the Board (the U.S. flag, the Navy flag, the Admiralty seal, and the Great Seal with a reverse)], and therefore cannot claim the sole merit of them and not entitled in this respect to the full sum charged." This is most probably a reference to his work as a consultant to the second committee that worked on the Great Seal of the United States. Therefore, he would not be eligible to be paid for the Great Seal.

On September 24, 1789, President George Washington nominated Hopkinson to the newly created position of judge of the United States District Court for the Eastern District of Pennsylvania. He was confirmed by the United States Senate, and received his commission, on September 26, 1789.

Other notable essays are "Typographical Method of conducting a Quarrel", "Essay on White Washing", and "Modern Learning". Many of his writings can be found in Miscellaneous Essays and Occasional Writings, published at Philadelphia in three volumes in 1792 (see Bibliography).

Francis Hopkinson provided assistance to the second committee that designed the Great Seal of the United States. On today's seal, the 13 stars (constellation) representing the 13 original states have five points. They are arranged in a larger star that has six points. The constellation comprising 13 smaller stars symbolizes the national motto, "E pluribus unum." Originally, the design had individual stars with six points, but this was changed in 1841 when a new die was cast. This seal is now impressed upon the reverse of the United States one-dollar bill. The seal, designed by william Barton, contains an unfinished pyramid with a radiant eye, an image used by Hopkinson when he designed the continental $50 currency bill.

The legend of Betsy Ross as the designer of the first flag entered into American consciousness about the time of the 1876 centennial celebrations, owing to the efforts of her grandson, william Canby. This flag with its circle of 13 stars came into popular use as a flag commemorating the nation's birth. Many Americans today still cling to the Betsy Ross legend that she designed the flag, and most are unaware of Hopkinson's legacy. The circle of stars (a circle connotes eternity) first appeared after the war ended and after Hopkinson’s original design.

There is no known Sketch of a Hopkinson flag—either U.S. or naval—in existence today. Hopkinson, however, did incorporate elements of the two flags he designed in his rough sketches of the Great Seal of the United States and his design for the Admiralty Board Seal. The rough Sketch of his second Great Seal proposal has 7 white stripes and 6 red stripes. The impression of Hopkinson’s Admiralty Board Seal has a chevron with 7 red stripes and 6 white stripes. The Great Seal reflects Hopkinson’s design for a governmental flag and the Admiralty Board Seal reflects Hopkinson’s design for a naval flag. Both flags were intended to have 13 stripes. Because the original stars used in the Great Seal had six points, Hopkinson's U.S. flag might also have intended the use of 6-pointed stars. This is bolstered by his original Sketch that showed asterisks with six points.

In the letter, Hopkinson noted that he hadn’t asked for any compensation for the designs, but was now looking for a reward: "a Quarter Cask of the public Wine." The board sent that letter on to Congress. Hopkinson submitted another bill on June 24 for his "drawings and devices." The first item on the list was "The Naval Flag of the United States." The price listed was 9 pounds. This flag with its red, outer stripes was designed to show up well on ships at sea. A parallel flag for the national flag was most likely intended by Hopkinson with white, outer stripes as on the Great Seal of the United States and on the Bennington flag, which commemorated 50th anniversary of the founding of the United States (1826). Ironically, the Navy flag was preferred as the national flag.