The towns of Old La Sal and Coyote also sprang at the base of the mountain range because of its water and location on the southern Colorado-Utah mail route. Farming, ranching, and mining on or near the mountains gave spurts of growth to nascent industries as did also the Denver and Rio Grande Western Railroad that passed through Thompson seventy-five miles north of Moab. Cattle, sheep, and agricultural produce made their way through the canyons and sagebrush flats to both eastern and western markets.

Although there were mining strikes in 1892 in the La Sals and other nearby mountains and rivers, cattle and timber proved to be of more lasting economic benefit. The Pittsburgh Cattle Company started in the mid-1880s and ran as many as 20,000 head of livestock on the mountains until the company sold out to the La Sal Cattle Company in 1895. Lemuel H. Redd and other stockmen from Bluff continued to range cattle there, until eventually Charles Redd assumed control of the entire operation. Redd Ranches continues to use the La Sals to this day.