Bowie migrated with his parents to Missouri (1800) and then to Louisiana (1802). At 18 he left home, clearing land and sawing timber for a living. Later he reportedly engaged in the slave trade with his brothers John and Rezin. With the latter he also bought and improved a sugar plantation in Louisiana, where he served for a time in the state legislature and spent much time in New Orleans society.

After he reportedly killed a man in a duel, Bowie went to Texas about 1828, where at Bexar (now San Antonio) he became friendly with the Mexican vice governor, Juan Martín de Veramendi. He assumed Mexican citizenship, acquired land grants, and married Veramendi's daughter, Ursula (1831). He was one of thousands of U.S. settlers and adventurers who swelled the non-Mexican population in Texas, and restrictive Mexican legislation to curb the newcomers soon interested him in the Texas revolutionary movement. As a colonel in the Texas army, he fought with distinction in several battles and finally joined Col. William B. Travis in the gallant defense of the Alamo, an abandoned mission house in San Antonio. Already confined to his cot by illness, Bowie was killed with the other defenders when the Alamo finally fell to numerically superior Mexican forces.

Bowie's daring and courage have become legendary through Western song and ballad. His name is also associated with the Bowie knife, a weapon (sometimes called the “Arkansas toothpick”) invented by either him or his brother Rezin.