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. A large amount of the alignment is on former US 87, but several portions through built-up areas have been bypassed, as well as two longer areas where US 87 still follows the old road.
The Interstate begins at a point along the four-lane US 87 freeway south of downtown Lubbock. Mile 0 is posted near 77th Street, about five blocks south of Loop 289. Exit numbering begins just to the south, with exit 1 at the 82nd Street interchange; the freeway becomes six lanes at its north end. The Loop 289 interchange is a cloverleaf between the one-way frontage roads of each highway, and with direct ramps from I-27 south to Loop 289 west (exit 1A) and Loop 289 east to I-27 north. U.S. Highway 84 (Avenue Q and Slaton Highway) crosses I-27 at a split diamond interchange, with an extra approach from the northeast carrying U.S. Highway 87 Business (Avenue A) into the junction. Exit 1B connects I-27 south to US 84 and the Loop 289 frontage roads, while all traffic from US 87 north to US 84, US 87 Business, or Loop 289 must use exit 1 for 82nd Street.
The six-lane cross section that began at exit 1 remains through Lubbock. Major junctions in that city include U.S. Highway 62/State Highway 114 (19th Street, exit 3) and U.S. Highway 82 (4th Street, exit 4), which is also the north end of US 87 Business. Between these two interchanges, the frontage roads temporarily end as I-27 crosses over a rail line. Spur 326 (Avenue Q) merges with I-27 at exit 6A, and exit 6B is a split diamond with Loop 289. The outer lanes leave at Farm to Market Road 2641 (Regis Street, exit 8), reducing I-27 to two lanes in each direction as it passes Lubbock International Airport and leaves the city.
I-27 crosses over the Plainview Sub for the first time north of Farm to Market Road 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. Old US 87 between exits 13 and 15 is now Loop 461; at exit 15, I-27 begins to parallel the rail line, just to its west. Along this part of the highway, and other similar portions, slip ramps still connect the main lanes with the frontage roads, but intersecting roads pass over all four roadways and the railroad on a long bridge; a pair of two-way roadways connects the frontage roads to the crossroad, with the one on the east crossing the railroad at-grade.
As it approaches Abernathy, I-27 curves west away from the Plainview Sub. The old main road through the city, between exits 20 and 22, is now Loop 369; I-27 passes through 1.5 blocks to the east. Despite I-27's location north of Abernathy, 1/2 mile (1 km) west of the rail line, all interchanges between Abernathy and Hale Center, except the one at Farm to Market Road (exit 24), use the same configuration where the intersecting road crosses over all roadways. Approaching Hale Center, I-27 curves northeast as it splits from Farm to Market Road 1424 (exit 36) at a simple diamond interchange. The freeway passes through the city one block east of the old road, now I-27 Business, which is accessed at exits 36 and 38. As it leaves Hale Center, I-27 turns to the northeast, following the northwest side of the rail line.
The next two interchanges along the railroad between Hale Center and Plainview use the same style, in which the crossroad goes over everything. I-27 Business splits at exit 45, a modified Y interchange, to pass through Plainview, and I-27 travels west of that city on a bypass. The two outer interchanges on this bypass, Farm to Market Road 3466 (exit 48) and Quincy Street (exit 51), are handled in the same way as the interchanges along the railroad, but the other two, U.S. Highway 70 (exit 49) and State Highway 194 (exit 50), are standard diamonds. Between exits 49 and 50 is another overpass over the frontage roads - 24th Street - with no separate slip ramps. I-27 Business ends at a trumpet interchange (exit 53) north of Plainview, where I-27 again begins to parallel the Plainview Sub to the west. Both interchanges between this one and the first split with US 87 (exit 61), a modified Y south of Kress, continue the pattern with the crossroad bridging over everything.
After it leaves US 87, I-27 is no longer next to the rail line, but it continues to handle interchanges as it does alongside the line, except at State Highway 86 (exit 74), a standard diamond that serves Tulia. US 87 rejoins the freeway at a modified diamond (exit 77) north of Tulia, at which I-27 crosses to the east side of the Plainview Sub before paralleling it to that side. After several of the typical interchanges adjacent to the railroad, US 87 splits again at a modified Y (exit 88) south of Happy. Except for the northernmost one, all of the interchanges on the bypass of Happy and Canyon are diamonds; there is a break in the frontage road north of Farm to Market Road 3331 (exit 108), where I-27 crosses the Prairie Dog Town Fork of the Red River. Exits 109 (Buffalo Stadium Road) and 110 (US 87 south, US 60 west) are integrated, with some access to one road provided via the other.
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. Several near the south end are handled by bridging the intersecting road over all roadways, but, once I-27 crosses Loop 335 (exit 116), almost all interchanges are diamonds. At exit 119A, which marks the south end of the six-lane cross section in Amarillo, Hillside Road passes under both the main lanes and the frontage roads, with two ramps providing partial access. Other connections with Hillside Road are made via Western Street (exit 119B), which crosses the frontage roads at grade. The end of I-27 at Interstate 40 (exit 123B) is a fully-directional turbine interchange; U.S. Highway 287 also passes through, using I-40 to the east and US 60/US 87 to the north. Four lanes continue beyond I-40, and are joined by several from the I-40 ramps, making the northernmost portion of the Canyon Expressway five lanes in each direction. Several blocks beyond I-40, the highway ends at a split into two one-way pairs. Northbound traffic feeds onto Fillmore Street (US 87 north) and Buchanan Street (US 60 east and US 287 north), while southbound traffic approaches on Taylor Street (US 287 south) and Pierce Street (US 60 west and US 87 south). The rightmost of the five northbound lanes is barrier-separated from the rest, forcing traffic exiting I-40 west onto Buchanan Street. Through the I-40 interchange and the split, the frontage roads are discontinuous.