White studied law in Lancaster, Pennsylvania, under James Hopkins, and was admitted to the bar in 1796. Two years later, he married Elizabeth Carrick, the daughter of his mentor, Samuel. In 1801, White was appointed judge of the Superior Court of Tennessee, then the state's highest court. In 1807, he resigned after being elected to the state legislature. He left the state legislature in 1809, following his appointment to the state's Court of Errors and Appeals (which replaced the Superior Court as the highest court). He resigned this position in 1815, when he was elected to the state senate. He served in the state senate until 1817. As a state legislator, White helped reform the state's land laws, and engineered the passage of an anti-dueling measure. In 1812, White was named president of the Knoxville branch of the Bank of Tennessee. White was described as a very cautious banker, and his bank was one of the few in the state to survive the Panic of 1819. In 1821, President James Monroe appointed White to a commission to settle claims against Spain, following the Adams-Onís Treaty in which that nation sold Florida to the United States. In 1825, the Tennessee state legislature chose White to replace Andrew Jackson in the United States Senate (Jackson had resigned following his failed run for the presidency in 1824). White spearheaded the Southern states' opposition to sending delegates to the 1826 Congress of Panama, which was a general gathering of various nations in the Western Hemisphere, many of which had declared their independence from Spain and abolished slavery. White argued that if the U.S. attended the congress, it would violate the commitment to neutrality put forth by President Washington decades earlier, and stated that the nation should not get involved in foreign treaties merely for the sake of "gratifying national vanity." Following Jackson's election to the presidency in 1828, White became one of the Jackson Administration's key congressional allies. White was chairman of the Senate Committee on Indian Affairs, which drew up the Indian Removal Act of 1830, a major initiative of Jackson. The act called for the relocation of the remaining Native American tribes in the southeastern United States to territories west of the Mississippi River, and would culminate in the so-called Trail of Tears. In an 1836 speech, White described himself as a "strict constructionist," arguing that the federal government could not pass any laws outside its powers specifically stated in the Constitution. Like many Jacksonians, he was a staunch states' rights advocate.