Gaines was born September 22, 1795 in Augusta County, Virginia, to Abner Gaines and Elizabeth Mathews. His grandfathers and great-grandfather served during the American Revolutionary War. He received an education and studied law, and volunteered in the War of 1812. He was a lawyer with his practice in Boone County, Kentucky. He was a state legislator in Kentucky during the 1820s and 1830s. He volunteered and was appointed the rank of "Major" during the Mexican-American War in 1846. He and some 80 soldiers were captured at Incarnation in January 1847. They were held captive in Mexico City until August.

While a prisoner, he was elected him to the 30th United States Congress from Kentucky's 10th Congressional District. At the end of his term as congressman he returned to Boone County, and in October of 1849 he accepted the position of Governor of the Territory of Oregon. He was a supporter of President Zachary Taylor, who was elected in 1848. The Taylor administration rewarded Gaines by appointing him to be the Oregon territorial governor.

From the start, Gaines's tenure in office proved to be difficult. He arrived in the territory by ship, losing two of his daughters to yellow fever along the way in Panama. Shortly after arriving in the territory, his wife died after falling off a horse, and the governor soon lost his son. His political life would prove to be just as turbulent.

His tenure was marked with fierce partisanship, facing opposition from the press and the Democrat-controlled territorial legislature. Gaines unsuccessfully tried to keep the territorial capital at Oregon City, Oregon. The governor also pushed for other Whig policies that were at often at odds with popular sentiment. These unpopular positions, coupled with fierce partisanship, cemented a perception that Gaines was an Easterner, out of touch with Pacific Coast needs and attitudes.

In 1853, Gaines left office, succeeded by the Democrat Joseph Lane, who assumed the reins of government for three days. Undeterred by the past hostilities of the Oregon electorate, he chose to stay in Oregon, remarrying and settling in a farm just outside Salem, Oregon. In 1854 he and two of his sons (Archibald & Abner) drove over 200 head of cattle from Kentucky and Arkansas across the plains to Oregon. 35 of these were pure bred Durham.

Gaines ran for the U.S. House of Representatives in 1855, but lost to Lane. Governor Gaines' appointment to the governorship cost him the death of several of his family. Two daughters (Harriet & Florella) in 1850 in Brazil, his wife (Elizabeth) in 1851 in a fall from a horse, at which time his remaining children were sent back to relatives in the east. His daughter Matilda died in Tennessee in the spring of 1857. He died December 9, 1857 and is interred in the Old Pioneer Cemetery at Salem, Oregon.