Adrian is situated along Interstate 40 (Old Route 66) in south central Oldham County, approximately 47 miles (76 km) west of Amarillo.

[4] Adrian is the geo-mathematical midpoint of Route 66, positioned 1,139 miles (1,833 km) from both Chicago, Illinois and Los Angeles, California.

Adrian, Texas bills itself as the midway point between Chicago and Los Angeles on historic Route 66 with signage proudly declaring "← Los Angeles 1139 miles — Chicago 1139 miles →" to travellers on the old highway who arrive from as far afield as Europe.

[6] The "US 66 midpoint" branding was adopted in 1995 on the advice of travel author and Route 66 Association founder Tom Snyder.

[10][11] The café, built in 1928[12] and located between a motel and a former filling station, operated 24 hours a day during Route 66's heyday.

[6] The long-closed Bent Door Café and trading post, built by Bob Harris in 1947 on the site of the 1940s Kozy Kottage Kamp, incorporates portions of a former air traffic control tower decommissioned after World War II; the tower windows originally slanted toward the runway, so the door is bent to match.

The community originated in 1900, when the Rock Island Railroad survey marked the site as a future station and shipping point.

The Iowa-based American-Canadian Land and Townsite Company attracted prospective farmers and businessmen to the community.

The slow growth rate was attributed to a lengthy drought and the difficulty of maintaining a sufficient water supply.