The Santa Fe Trail was an important route in the western United States, leading from Missouri to Santa Fe, New Mexico.

In 1821 William Becknell organized the first party to trade in New Mexico. By 1850 a monthly stagecoach line was established between Independence, Missouri and Santa Fe (earlier beginnings of the trail were Franklin and Westport). The arrival of the railroad in Santa Fe in 1880 marked the end of the Santa Fe Trail.

Part of the route has been designated a National Scenic Byway.

A dramatization of life on the route was made into a motion picture in 1941, starring Errol Flynn, Olivia de Havilland, Raymond Massey and Ronald Reagan.