The Spanish Trail literally began northwest of Santa Fe at Abiquiu, the last European settlement during the trail days; between New Mexico and the frontier outpost of Cucamonga in California was a distance of about a thousand miles. In Colorado, the trail passed through or near Ignacio, Durango, Dolores, and Dove Creek. It crossed into Utah near the tiny settlement of Ucolo, about fifteen miles east of Monticello.

In order to head the great canyons of the Colorado and Green rivers, the Spanish Trail held to a northwest course as far as the present town of Green River. From Green River, the trail crossed the northern part of the San Rafael Swell, missing its rugged interior. From here, the trail carried early travelers on an easy course along the wide, well-watered floor of Castle Valley, and then crossed the Wasatch Plateau to continue through the Great Basin, via Sevier River Valley, the Markagunt Plateau, the Parowan Valley, and the Escalante Desert. On the southern edge of the Escalante Desert, the trail passed up Holt Canyon to Mountain Meadows, a favorite resting place, known in the trail days as "Las Vegas de Santa Clara." Leaving the meadows, the trail turned down the tributaries of Magotsu Creek and Moody Wash to the main Santa Clara River, through the homeland of the Southern Paiute Indians.