Born in Belmont, Virginia, he attended school in Maryland and served in the War of 1812. He moved to St. Louis, Missouri Territory in 1814 and there studied law, earning admittance to the bar in 1817, and serving as a U.S. Attorney from 1821 to 1826.

His first foray into politics came in 1822, when he was elected to the Missouri House of Representatives. He moved up to the United States House of Representatives for a single term (1827-1829), then returned to Missouri to sit in the State Senate from 1831 to 1835, then again in the Missouri House from 1835.

Bates became a prominent member of the Whig Party during the 1840s. President Millard Fillmore asked him in 1850 to be U.S. Secretary of War, but Bates declined. At the Whig National Convention in 1852, Bates was considered for the vice-presidential slot on the ticket, and he led on the first ballot before losing on the second ballot to William Alexander Graham.

After the breakup of the Whig Party in the 1850s, Bates became a Republican, and was one of the three main candidates for the party's 1860 presidential nomination, which was won by Abraham Lincoln. The next year, after winning the election, Lincoln appointed Bates as his Attorney General, an office Bates held from 1861 until 1864. Bates was the first Cabinet member to hail from the region west of the Mississippi River.

Bates returned to Missouri after leaving Lincoln's cabinet. He died in St. Louis in 1869.