Thomas Fitzsimons was born at Ballikilty, County Wexford, Ireland in October of 1741 to Anthony Fitzsymons in the mid-1750s.  We know his mother's name was Jane, but we do not have a record of her maiden surname.  Fitzsimons immigrated to Philadelphia where his father soon died. However, he had enough education that he could begin work as a clerk in a mercantile house. He married Catherine Meade on November 23, 1761 and formed a business partnership with her brother George. Their firm specialized in the West Indies trade, which would successfully operate for over 41 years. However, this firm was soon hit by the new revenue measures created to help support the finances of the British Empire, including the much reviled Stamp Act of 1765. Concerned with these ideas, Fitzsimons became active in the Irish merchant community in Philadelphia, elected the head of the Friendly Sons of St. Patrick in 1771 and later, in 1774, a steering committee organized to protest the Coercive Acts.

When Pennsylvania began mobilizing and organizing a militia to fight the British, Fitzsimons was soon involved. He served as captain of a company of home guards, which he raised. His company served as part of the soldiers who manned posts along the New Jersey coast to defend against British actions. His unit later served as part of the reserve at the Battle of Trenton in 1776. Later in the war, Pennsylvania's government asked him to head a board to oversee the newly formed Pennsylvania Navy. Under this role, he helped organize the strategic resources of Pennsylvania, and later provided supplies, ships, and money in support of Pennsylvanian and French forces.

Fitzsimons entered active politics as a delegate to the Continental Congress. He was a member of Pennsylvania's House of Representative. He was also a delegate to the U.S. Constitutional Convention. Although not a leading member of that convention, he supported a strong national government. the end of slavery, the United States Congress's powers to impose a tariff on imports and exports, the granting the house of representatives, and the equal power in making treaties to the United States Senate in making treaties. He was one of only two Catholic signers of the United States Constitution, the other being Daniel Carroll of Maryland.

After the constitution was established, he served in the first three sessions of the House of Representatives but finally failed to win re-election. This was partially attributed not to Fitzsimons's own fault but to public opinion turning against the Federalist Party, to which he belonged in the wake of the Whiskey Rebellion's suppression.

While withdrawing from politics, Fitzsimons remained active in civic and business affairs. He served as president of Philadelphia's Chamber of Commerce, as a trustee of the University of Pennsylvania, Director of the Delaware Insurance Company and a director of the Bank of North America from 1781-1803. He was a founder of the bank, and supported efforts to found the College of Georgetown.

Thomas died on August 26, 1811 in Philadelphia, where he was buried in the cemetery of St. Mary's Catholic Church, which is in present Independence National Historical Park.