Using the route below, Los Angeles to Santa Fe (New Mexico) is around 850 miles. It'll take at least 12.5 hours to drive without fuel, food and rest stops or any issues caused by traffic congestion, road construction or navigation errors. 1. Take I-10 east until it meets I-15. Go north on I-15. 2. Follow I-15, passing through or near e.g. Cajon Junction and Victorville. 3. Leave I-15 at Barstow and go east on I-40. 4. Follow I-40 east, passing through or near e.g. Kingman, Williams, Flagstaff, Holbrook (Arizona) and Gallup until it meets I-25 in Albuquerque. Take I-25 north. 5. Follow I-25 to Santa Fe. Note that long stretches of the route have little or no habitation so you'll need to plan fuel, food and rest stops carefully.