Interstate 35 (I-35) is a major north–south Interstate Highway that runs from Laredo, Texas near the Mexican border to Duluth, Minnesota. In Texas, the highway begins in Laredo and runs north to the Red River north of Gainesville, where it crosses into Oklahoma. Along its route, it passes through the cities of San Antonio, Austin, and Waco before splitting into two branch routes just north of Hillsboro: I-35E heads northeast through Dallas, while I-35W turns northwest to run through Fort Worth. The two branches rejoin in Denton to again form I-35, which continues to the Oklahoma state line. The exit numbers for I-35E maintain the sequence of exit numbers from the southern segment of I-35, and the northern segment of I-35 follows on from the sequence of exit numbers from I-35E. I-35W maintains its own sequence of exit numbers.

In Texas, I-35 runs for just over 503 miles (810 km), which does not include the 85-mile (137 km) segment of I-35W. It does include the 97-mile (156 km) segment of I-35E. Texas contains more miles of the overall length of I-35 than any other state, almost one-third of the entire length.

The Interstate is currently undergoing an extensive renovation and expansion project, known as "My35". The project includes work on portions of the Interstate from Dallas south to Laredo. Once complete, the highway will span three lanes in each direction from Hillsboro to San Antonio.

I-35 has been designated the Texas portion of the Purple Heart Trail. Signage noting this designation is being added along the route.

In Laredo, I-35 is between six and eight mainlanes in each direction, dropping to four near milemarker 13. After running concurrently with U.S. Highway 83 (US 83) for 20 miles (32 km), the highway continues north-northeast across the South Texas Plains. The highway passes through the cities of Cotulla, Dilley, Pearsall, Devine, and Lytle before reaching San Antonio.

In San Antonio, I-35 is listed as the PanAm Expressway. It starts out as four lanes from the south until it reaches State Highway 422 Spur (Spur 422, Poteet-Jourdanton Freeway), expanding to six to eight mainlanes of travel. Its southern point begins in the southwest corner of town and travels northeast, crossing I-410 near its southwest point. At the southwest corner of Downtown, it reaches an intersection with I-10, US 87, and US 90. US 90 continues east and west from this junction, while I-10 westbound/US 87 northbound joins with I-35 northbound along the westside of Downtown. In this section, it splits lanes to form two levels, a lower one for local traffic and a higher one for express traffic. They briefly rejoin near the northwest corner of Downtown to allow I-10/US 87 to split off and go northwest.

I-35 continues, resplitting lanes again as it curves around the northwest corner of Downtown and turns east. It rejoins the lanes as it goes through an intersection at the northeast corner of Downtown, where I-37's northern terminus is located, while US 281 will continue on the north–south freeway. I-35 continues east for a few miles until it begins to curve back to the northeast. It merges with I-410 on its eastern north–south leg from its northbound direction in a triangular interchange and continues north concurrently from there. A few miles later, I-410 will split off onto its northern west–east leg, while I-35 resumes its north-northeast course past the northeast corner of the city.

Trucks are restricted from travel in the far left lane of I-35 in either direction throughout the San Antonio area. The restriction covers Bexar, Guadalupe, and Comal counties.