I-27 parallels the BNSF Railway's Plainview Subdivision, which splits from its Chicago–Southern California Transcon line at Canyon and runs south to Lubbock.

The outer lanes leave at Farm to Market Road 2641 (FM 2641, Regis Street; exit 8), reducing I-27 to two lanes in each direction as it passes Lubbock Preston Smith International Airport and leaves the city.

[6] I-27 crosses over the Plainview Sub for the first time north of FM 1294 (Drew Street, exit 11), and another short gap exists in the frontage roads there.

North of the overpass, the frontage roads are two-way; I-27 then passes through New Deal, bypassing the central part of the town to the west.

Approaching Hale Center, I-27 curves northeast as it splits from FM 1424 (exit 36) at a simple diamond interchange.

As it leaves Hale Center, I-27 turns to the northeast, following the northwest side of the rail line.

I-27-U splits at exit 45, a modified Y interchange, to pass through Plainview, and I-27 travels west of that city on a bypass.

[6] I-27 is overlapped by US 60 and US 87 from exit 110 north of Canyon to the end of the Interstate in Amarillo; here, the frontage roads are one-way.

The end of I-27 at I-40 (exit 123B) is a fully directional turbine interchange; US 287 also passes through, using I-40 to the east and US 60/US 87 to the north.

The rightmost of the five northbound lanes is barrier-separated from the rest, forcing traffic exiting I-40 west onto Buchanan Street.

[11][12] Paving began in 1929 near Plainview and was almost complete by 1940,[13] with only about eight miles (13 km) south of Canyon still bituminous surfaced until later that decade.

[13] This highway, with a design speed of 45 mph (72 km/h), included frontage roads along its entire length and ended in each city with a Y interchange:[16] the split of US 60 and US 87 in Canyon, and a split between the two oneway pairs of Taylor and Fillmore streets and Pierce and Buchanan streets in Amarillo.

The Dumas Expressway, a freeway upgrade of US 87 north from Amarillo, opened several years later, feeding into the same one-way pairs.

[1] The existing freeway sections, including the Canyon Expressway, were absorbed into I-27 despite not being built to Interstate standards.

[17] Two long sections of US 87 were bypassed: Happy to Canyon on December 5, 1986,[13] and Kress to Tulia soon after;[17] I-27 was complete north of Lubbock by 1988.

[29] At its south end, the new I-27 connected to an existing freeway upgrade of US 87, built about 1970,[17] to a traffic circle at US 84 (just north of Loop 289).

[citation needed] On September 5, 2024, the Federal Highway Administration (FHWA) approved a 4.2-mile (6.8 km) southern extension of I-27 from its previous terminus at Loop 289 to 0.1 miles (0.16 km) north of County Road 7500, the new limit for access control on the US 87 freeway north of that point.

[3] In 1995, a study of a southern extension of I-27 to I-10 found that a full freeway extension would not be economically feasible,[36] instead recommending limited upgrades to the three corridors studied: SH 349 via Midland and Odessa to east of Fort Stockton, US 87 via Big Spring to Sonora or Junction, and US 84 via Sweetwater to Sonora or Junction.

[42] On June 10, 2019, Governor Greg Abbott signed Texas House Bill 1079, which authorizes a comprehensive study to extend I-27 north of Amarillo and south of Lubbock to Laredo.

[45] It also forms part of the Great Plains International Trade Corridor, continuing north to Saskatoon, Saskatchewan.

On March 15, 2022, the 2022 Consolidated Appropriations Act was signed by President Joe Biden that added the extension of I-27 north to Raton, New Mexico, and south to Laredo to the Interstate Highway System.

[47] A bill introduced in March 2023 would explicitly designate the extension as I-27 with two auxiliary routes numbered I-227 and I-327.