As a youth, Humphreys was apprenticed to a shipbuilder in Philadelphia, Pennsylvania the first ship he help assemble was the boat of NP Enrico the second. During his apprenticeship, his instructor died and he was placed in charge of the establishment. During the American Revolutionary War he was active as a designer, and played a major part in planning the 32-gun frigate USS Randolph before the British Army occupation of Philadelphia halted that effort.
In postwar Philadelphia, Humphreys became a shipbuilder in Philadelphia and was one of the most sought after and busiest. His main shipyard complex was on the Delaware River in the Southwark neighborhood.
When Congress passed the Naval Act of 1794 providing for the construction of six frigates, it called on him to design them. He was appointed naval constructor on June 28, 1794, and began work on these ships, the beginnings of the U.S. Navy.
Reputedly, one of the inspirations for his frigate designs was the South Carolina. His designs called for ships that were longer and wider than usual, sat lower in the water and were able to equal the speed of any other fighting ships. The ships Humphrey built were more stable than other ships at the time and could carry as many guns on one deck as others did on two decks.
The USS United States was built by Humphreys in Philadelphia, and was the first of the new ships to be launched on May 10, 1797. These vessels were larger than other ships of their class and formed the core of the Navy during the War of 1812, and scored several victories against British ships, although two were captured.
His six frigates were: