Fitzsimons' family immigrated to Philadelphia in the mid-1750s. His father died shortly thereafter; young Thomas, upon completing his education, entered a counting-house as a clerk.  In 1763 Thomas went into business with his new brother-in-law, George Meade (the grandfather of the Civil War general), specializing in trade with the West Indies. 
Due to the strong pacifist beliefs of its resident Quakers, Pennsylvania lacked a standing militia at the onset of the Revolutionary War. Consequently, the Patriots had to build the Pennsylvania military from the ground up, fielding volunteer units called Associators. Fitzsimons raised and commanded a company in Colonel John Cadwalader's 3d Battalion. Following the British attack on New York in 1776, Fitzsimons' company served in the cordon of outposts that guarded the New Jersey shoreline.
The attack on New York proved successful, and the British next turned their attention to New Jersey, forcing the outnumbered Patriots to withdraw beyond the Delaware River. Fitzsimons' company went on duty on 5 December to cover the continentals' retreat. For the remainder of the month it guarded the river's Pennsylvania shore. Although Fitzsimons' unit did not participate in Washington's Christmas Eve attack on Trenton, they did assist in dealing with a British counterattack on January 2. Following the withdrawal of the British from most of New Jersey, Fitzsimons retired from active duty. 
Fitzsimons was appointed to the Continental Congress in 1782, where he played a key role in developing a centralized economy. A strong advocate of private ienterprise, Fitzsimons promoted the growth of domestic industry and the payment of government debts. However, he was opposed to heavy taxes, particularly those that would "...fall too heavily on any particular part of the community." While his evenhandedness won him respect in Congress, it also brought criticism from Pennsylvania voters who felt that he was not being active enough in serving their interests. Fitzsimons resigned from Congress in 1783. 
Fitzsimons was asked to represent Pennsylvania at the Federal Constitutional Convention in 1787. There, he argued strongly that the Federal government should have the ability to tax imports and exports. Following the Convention, he was instrumental in advocating its ratification.
Later Political Service
Fitzsimons was elected as a Pro-Administration candidate to the First, Second, and Third Congresses, serving in the House of Representatives for six years; during this time, he chaired the Ways and Means Committee.
Thomas Fitsimons died in Philadelphia, Pennsylvania, on August 26, 1811. He was buried in St. Mary’s Roman Catholic Churchyard.