Born on October 31, 1740, in Abingdon, Province of Maryland, British America, Paca entered school at the Philadelphia Academy and Charity School in 1752, and went on to attend the College of Philadelphia (now the University of Pennsylvania), graduating in 1759 with a Bachelor of Arts degree. He was also to receive a Master of Arts degree from the same institution in 1762, though this required no further study, only that Paca request it and be in good standing. He also attended the Inner Temple in London, England and read law in 1761, with Stephen Bordley and was admitted to the bar that year. He entered private practice in Annapolis, Province of Maryland starting in 1763. He was a member of the lower house of the Maryland Proprietary Assembly from 1767 to 1774. He was a delegate to the First Continental Congress and the Second Continental Congress from Maryland from 1774 to 1779. He was a signer of the United States Declaration of Independence in 1776. He was a member of the Maryland Senate from 1776 to 1777, and from 1778 to 1780. He was a Judge of the Maryland General Court in 1778. He was a Judge of the Court of Appeals in Cases of Capture from 1780 to 1782. He was Governor of Maryland from 1782 to 1785. He was a member of the Maryland House of Delegates in 1786. He was influential in establishing Washington College in Chestertown, Maryland in 1786. He was a delegate to the Maryland convention in 1788 which ratified the United States Constitution.

Paca was the child of John Paca (c. 1712 – 1785), a wealthy planter in the area of Italian heritage, and his wife Elizabeth Smith (?-c. 1766). He was the second son of the family, after his elder brother Aquila, and had five sisters. He courted Mary Chew, the daughter of a prominent Maryland planter, and they were married on May 26, 1763. They had three children, though only their son John Philemon survived into adulthood.

Paca received a recess appointment from President George Washington on December 22, 1789, to the United States District Court for the District of Maryland, to a new seat authorized by 1 Stat. 73. He was nominated to the same position by President Washington on February 8, 1790. He was confirmed by the United States Senate on February 10, 1790, and received his commission the same day. His service terminated on October 13, 1799, due to his death at his estate of Wye River, in Queen Anne’s County, Maryland and was interred in a family cemetery on the estate.

According to Stanley South, “[t]he rumor that the name was Italian came from a remark made in 1911 by James Cardinal Gibbons of Baltimore, who commented that he thought a relationship existed between Paca and the Italian family Pecci”. In a July 18, 1937, letter to the New York Times, a self-described descendant of Paca claimed:

Paca’s Annapolis home, the Paca House and Garden, was added to the National Register of Historic Places and designated a National Historic Landmark in 1971. The William Paca Club in New Providence, New Jersey is named in his honor. The Club cites the fact that Paca was the only Italian-American to sign the Declaration of Independence as the reason for bestowing him this honor. Paca-Carroll House at St. John’s College is named for Carroll and his fellow signer of the Declaration of Independence, William Paca.