The Santa Fe Trail between Missouri and Santa Fe, in what was Mexico, ran through the southeast corner of Colorado. This reliable historic route was traversed by fortune-seeking individuals, including Wild Bill Hickok, frontiersman Kit Carson, Jedediah Smith and explorer Zebulon Pike. Begin your tour in Trinidad, a small city with a quaint Victorian downtown, where you can visit the historic Baca House, a grand adobe house that Felipe and Dolores Baca acquired for 22,000 pounds of wool in 1873, and the Bloom Mansion, part of the Trinidad History Museum.

As you head northeast on U.S. 350 through Comanche National Grassland, this area is full of life with falcons and hawks searching for prey, songbirds flitting from the grasses and antelope grazing in the meadows. In late summer, the roadside is inundated with sunflowers. For a worthy detour, follow the signs to Bent's Old Fort National Historic Site, founded in 1833 by brothers William and Charles Bent and their partner Ceran St.

Vrain, this reconstructed fort was a trading post strategically located between fur trappers in the Rockies, traders on their way to Santa Fe, and Cheyenne, Arapaho and Kiowa Indians who hunted in the area. Continuing on U.S. 50 heading east, you'll pass through the town of Las Animas and by John Martin Reservoir State Park, the second-largest body of water in the state. Two rare birds — the piping plover and the interior least tern — can be spotted along the shores of this lake in summer. The byway loosely follows the Arkansas River, leading you all the way to the town of Lamar and eventually to the Kansas–Colorado border, where it ends.