The highway begins in Corpus Christi at US 181 and SH 35 and heads north to San Antonio, where it ends at I-35.

It then heads west as a surface street for three blocks where it becomes entrance and exit ramps which connect to the freeway.

[5] I-37 begins officially at the gore point for these ramps, which is part of an interchange complex that also represents the southern ends of US 181 and SH 35.

The highway turns toward the northwest after the SH 358 interchange roughly parallel to the south of the Nueces River.

Just prior to leaving the Corpus Christi city limits, it intersects and has a short concurrency with US 77 (future I-69E).

It begins paralleling US 281 to the east before the two intersect at exit 72 and have a concurrency north of Three Rivers near Choke Canyon Reservoir.

The two routes remain concurrent until US 281 splits off at exit 104 northbound to head to Pleasanton, while I-37 bypasses the city to the east.

[7] As I-37 enters the San Antonio city limits, it intersects the northern terminus of US 181 at exit 132 southbound (this is according to the Texas Department of Transportation, or TxDOT; the American Association of State Highway and Transportation Officials, or AASHTO, extends US 181 northward to the northern terminus of I-37).

The highway intersects I-10, which is concurrent with US 90 and US 87, at exit 139 at a stack interchange on the southeastern corner of Downtown San Antonio.

[7] From I-410 to I-10 in San Antonio, I-37 is designated the Lucian Adams Freeway, after the World War II veteran.

Bordelon was the first San Antonio native to receive the Medal of Honor after being killed in action during WWII.

[11] No sections of US 281 were removed from the State Highway System as a result of the construction of I-37, but the two do share the same alignment at two different points between San Antonio and Three Rivers.

The $11-million (equivalent to $70.1 million in 2023[14]) project to construct the interchange with I-10 was at the time the largest single contract in the history of the state highway commission.

The freeway was completed from its southern terminus to 1.2 miles (1.9 km) to the west at the Port Avenue overpass to include the SH 286 interchange in 1963.

[16][17][18][19][20] In 1964, the freeway was extended another 1.1 miles (1.8 km) westward with the completion of the overpasses at Nueces Bay and Buddy Lawrence boulevards.

[34] The section from Steves Avenue north to Florida Street to include the I-10 interchange was also complete in 1967.