In 1843 the two men petitioned for and received a land grant of approximately 4 million acres (1,600,000 ha) located in what is now southeastern Colorado.

However, their plans for development of the area were halted due to the onset of the Mexican–American War, by which the United States invaded and acquired the Southwest and California.

Following the creation of the U.S. provisional government of New Mexico in 1847, St. Vrain organized a group of volunteers who fought alongside the US Army during the Taos Revolt.

After his father's death, Ceran became a clerk with Bernard Pratte and Company, a trading firm located in St Louis.

After establishing a trading post in Taos, St. Vrain travelled between Missouri and New Mexico for several years, including as far south as the Gila River (now in Southwest Arizona.

In 1830 St. Vrain was part of a caravan of traders on their way to Taos who were intercepted near the Canadian River by Colonel José Antonio Vizcarra (sometimes referred to as "Viscarra").

[9] They established company trading posts in Santa Fe and Taos, where their wagon trains made deliveries of goods shipped from Independence and Westport, Missouri.

Along the way, they forced the retreat of some 1,500 Mexican and Indian rebels, who took refuge in a thick-walled adobe church in Taos Pueblo.

During the Siege of Pueblo de Taos, Ceran St. Vrain's "Emergency Brigade" positioned themselves between the church and the mountains.

They cut off rebel forces attempting to escape the federal troops' artillery fire and frontal assault.

The mounted volunteers reportedly raided the rebels and killed a total of 51 Mexicans and Taos Indians in the fierce, close-quarter fighting that followed.