Thomas Fitzsimmons was born in Ireland in 1741 where his father provided him and his four siblings with an adequate education. His family immigrated to Philadelphia in 1760, where he began working as a clerk in a counting-house. The next year he married Catherine Meade, daughter of prominent local merchant, Robert Meade. Soon after, Fitzsimmons went into business with Catherine Meade's brother, forming George Meade & Company, specializing in the West India trade. While involving himself with his business, Fitzsimmons concurrently became engaged in politics. It began in 1771, when his fellow Irish merchants elected him the first vice president of the Friendly Sons of St. Patrick, a politically powerful fraternal association.

During the Revolutionary War, Fitzsimmons commanded a company of local volunteer militia. He also sat on the Philadelphia Committee of Correspondence, Council of Safety, and Navy Board. Fitzsimmons was intrigued by politics and continued involving himself in it. In September 1774, he went on to represent the city of Philadelphia in the First Continental Congress. He associated himself with Alexander Hamilton's program and the Federalist Party. The city continued sending him to the Continental Congress where he focused his attention on financial and commercial matters. After business distractions resulted in his resignation, he was elected to Pennsylvania's Council of Censors. In 1786, he began his first term in the state legislature. The next year, he was elected to represent the state at the Constitutional Convention. Although the U.S. National Archives and Records Administration note that Fitzsimmons did not make any outstanding contributions, he did sign his name to the Constitution. After serving in the First, Second, and Third Continental Congresses, he was unsuccessful in seeking re-election in 1794 to the Fourth.

Fitzsimmons contributed outside of his business and political life. He was one of the founders and directors of the Bank of America (no connection to the institution of the same name today) and a devoted philanthropist. As his company began suffering economic adversity in the latter part of his career, Fitzsimmons did not end his philanthropy. As a trustee of the University of Pennsylvania and a devoted Catholic, he contributed much of his life to these institutions.

After years of success and patriotism, Thomas Fitzsimmons died in Philadelphia on August 26, 1811. He was buried there in the graveyard at St. Mary's Roman Catholic Church, which is in present Independence National Historical Park. Today Fitzsimmons is most notable for his role as one of the founding fathers of this country.