Mangum began a law practice and entered politics.
He was elected to the United States House of Representatives, serving from 1823 to 1826.
After an interlude as a superior court judge, he was elected by the legislature as a Democrat to the Senate from North Carolina in 1830.

Mangum's stay in the Democratic Party was short.
He opposed President Andrew Jackson on most of the major issues of the day, including the protective tariff, nullification, and the Bank of the United States.
In 1834, Mangum openly declared himself to be a "Whig", and two years later, he resigned his Senate seat.

Due to a lack of organizational cohesion in the new Whig Party during the 1836 election, the Whigs put forward four presidential candidates: Daniel Webster in Massachusetts, William Henry Harrison in the remaining Northern and Border States, Hugh White in the middle and lower South, and Mangum in South Carolina.
Some optimistic Whigs foresaw the nomination of several candidates resulting in denying a majority of electoral votes to any one candidate and throwing the election into the House of Representatives, much like what occurred in 1824, where Whig representatives could then coalesce around a single candidate.
 This possibility, however, did not come to fruition and Democratic candidate Martin Van Buren won the election with an outright majority of electoral votes.
The legislature of South Carolina (which chose their electors until 1865) gave Mangum its 11 electoral votes.

After a four-year absence, Mangum served two more terms in the Senate, where he was an important ally of Henry Clay.
In 1842, he succeeded Samuel L. Southard as president pro tempore of the Senate, during a vice presidential vacancy.
Upon assuming office on May 23, he also became next in succession to the presidency, and remained so until the swearing in of George M. Dallas on March 4, 1845, a period which included President John Tyler's narrow escape from death in the USS Princeton disaster of 1844.
In 1852, he refused an offer to be a candidate for vice president on the Whig national ticket; fellow North Carolinian William Alexander Graham was nominated instead.

Realizing that he had little chance of being re-elected as the Whig Party broke up following the 1852 elections, Mangum retired in 1853 at the end of his second term.
In 1856 he, like many ex-Whigs, joined the nativist American Party, but a stroke soon afterward ended his political career.

Mangum died at his family estate in Red Mountain, an unincorporated area of Durham County, on September 7, 1861.
 He was buried in the family cemetery on his estate.
Mangum began a law practice and entered politics. He was elected to the United States House of Representatives, serving from 1823 to 1826. After an interlude as a superior court judge, he was elected by the legislature as a Democrat to the Senate from North Carolina in 1830.
Mangum's stay in the Democratic Party was short. He opposed President Andrew Jackson on most of the major issues of the day, including the protective tariff, nullification, and the Bank of the United States. In 1834, Mangum openly declared himself to be a "Whig", and two years later, he resigned his Senate seat.
Due to a lack of organizational cohesion in the new Whig Party during the 1836 election, the Whigs put forward four presidential candidates: Daniel Webster in Massachusetts, William Henry Harrison in the remaining Northern and Border States, Hugh White in the middle and lower South, and Mangum in South Carolina. Some optimistic Whigs foresaw the nomination of several candidates resulting in denying a majority of electoral votes to any one candidate and throwing the election into the House of Representatives, much like what occurred in 1824, where Whig representatives could then coalesce around a single candidate.  This possibility, however, did not come to fruition and Democratic candidate Martin Van Buren won the election with an outright majority of electoral votes. The legislature of South Carolina (which chose their electors until 1865) gave Mangum its 11 electoral votes.
After a four-year absence, Mangum served two more terms in the Senate, where he was an important ally of Henry Clay. In 1842, he succeeded Samuel L. Southard as president pro tempore of the Senate, during a vice presidential vacancy. Upon assuming office on May 23, he also became next in succession to the presidency, and remained so until the swearing in of George M. Dallas on March 4, 1845, a period which included President John Tyler's narrow escape from death in the USS Princeton disaster of 1844. In 1852, he refused an offer to be a candidate for vice president on the Whig national ticket; fellow North Carolinian William Alexander Graham was nominated instead.
Realizing that he had little chance of being re-elected as the Whig Party broke up following the 1852 elections, Mangum retired in 1853 at the end of his second term. In 1856 he, like many ex-Whigs, joined the nativist American Party, but a stroke soon afterward ended his political career.
Mangum died at his family estate in Red Mountain, an unincorporated area of Durham County, on September 7, 1861.  He was buried in the family cemetery on his estate.
Willie Person Mangum