After graduating from Princeton University, Sergeant served in the Philadelphia government and won election to the Pennsylvania House of Representatives.

In Congress, he supported Clay's American System and opposed the extension of slavery, voting against the Missouri Compromise.

He was elected as a Federalist to the United States House of Representatives to fill the vacancy caused by the death of Jonathan Williams.

He was re-elected three times, serving from October 10, 1815, to March 3, 1823, and managed to reach the position of chairman of the United States House Committee on the Judiciary.

[4] Sergeant was Henry Clay's running mate on the National Republican ticket during the 1832 presidential election but lost to Andrew Jackson and Martin Van Buren in a landslide and again retreated from public life.

After his vice presidential candidacy, he returned as president of the Pennsylvania constitutional convention in 1838, and then was elected as a Whig to the U.S. House of Representatives.

In 1844 he was considered for the Whig vice presidential nomination, to once again run with Clay, but the convention eventually selected Theodore Frelinghuysen.

Among his children were:[11] Sergeant died in Philadelphia on November 23, 1852, and was interred at Laurel Hill Cemetery Section L, Lots 1–7.