I-35 enters Oklahoma with U.S. Highway 77 (US-77) on a bridge over the Red River in Love County, south of Thackerville.

US-77 splits off at exit 1 (Red River Road) but parallels the Interstate for its entire length in Oklahoma.

After leaving Ardmore, it has a brief concurrency with State Highway 53 (SH-53) and enters Murray County and the Arbuckle Mountains.

This was in large part due to efforts of the towns of Wynnewood, Paoli, and Wayne fighting to keep I-35 as close as possible to US-77.

This was successful due to a threat from Governor Henry Bellmon to build a toll road rather than I-35, and legislation preventing state funds for the Interstate from being spent if it were more than one mile (1.6 km) from the U.S.

This stretch through the Arbuckles was particularly expensive and difficult to construct, taking almost two years and requiring the blasting and removal of 4 million cubic yards (3.1×10^6 m3) of rock.

[6] A few months later, in January 1971, I-35 was finally completed across the State of Oklahoma, when the remaining portions of the Interstate from Purcell to SH-7 near Davis were opened to traffic.

[3] In 2008, ODOT announced plans to widen two miles (3.2 km) of I-35 through Norman, from the Main Street interchange (exit 109) to the McCall Bridge over the Canadian River.

A public meeting held in Norman attracted 300 attendees, many bearing "Don't Close Lindsey" signs.

Attendees cited the impact on local businesses and those attending University of Oklahoma football games as grounds for opposing the closure of the interchange.

A second proposal would preserve access to Lindsey Street but require the seizure of a newly built Chevrolet dealership near the interchange.

The third proposal would instead send the ramps around the dealership, and the fourth, the highest-cost alternate, would use bridges to prevent Lindsey Street and SH-9 traffic from conflicting.

"[8] In early 2011, a solution was unveiled that would retain access to Lindsey Street and reconstruct the interchange without displacing the dealership.

[14] It was announced in February 2022 that the speed limit of the freeway would become 65 miles per hour (105 km/h) from 89th Street in Oklahoma City to just south of the SH-9 interchange in Norman.