Bypassed towns included Glenrio, Adrian, Vega, Conway, Groom, Jericho, Alanreed, McLean, and Shamrock; US 66 in each is retained as a business loop or spur of I-40.

Route 66 originally crossed from New Mexico into Texas at Glenrio, an unincorporated community founded in 1903 as a Rock Island Railroad siding.

[5] Amarillo is the only major city on the Texas portion of US 66; its 6th Street Historic District[6] includes a dozen buildings incorporating elements of Spanish Revival, Art Deco, and Art Moderne design including homes, service stations, a historic fire hall and a church.

The Ranchotel, a tourist court built in 1940 and designed architecturally to resemble a Texas ranch, was one of sixty-eight Route 66 lodgings operating in Amarillo by 1953.

[7] Eastbound alignments out of include one that parallels I-40 (where one can find the Steak Ranch), while another is along I-40 business, multiplexed with US Route 60 for several miles out of town.

[8] Conway is home to The Bug Farm (with five VW Beetles buried nose down) and a trading post; the Triangle Motel is as of 2012[update] being restored after years of resting closed, neglected and abandoned.

In Groom, Texas a leaning water tower stands empty, originally placed as an advertisement for a truck stop which burned years ago.