In Oklahoma, U.S. Highway 77 runs north-south, paralleling Interstate 35, connecting Texas to Kansas and running for 268 miles (431 km) through the central part of the state. It passes through many major cities, including Ardmore, Oklahoma City and its suburbs, Guthrie, and Ponca City. It has four lettered spur routes.
US-77 and SH-39 split off SH-74 to head eastbound along Washington St. in downtown Purcell. Together, they cross the James C. Nance Memorial Bridge into Lexington, where SH-39 splits off. It then heads through Slaughterville and Noble before entering Norman, becoming Classen Blvd., and later, Porter Ave. US-77 heads west along Robinson Ave. before heading north along Flood Ave. Flood then merges into I-35 northbound.
I-35 and US-77 remain together until the Fort Smith Junction in downtown Oklahoma City, where it transfers onto Interstate 235. At Interstate 44, I-235 ends, but US-77 continues northbound as a freeway, called the Broadway Extension. The Broadway Extension is a major freeway linking the downtown area to Edmond. In Edmond, it heads east to meet I-35, which it joins again until Guthrie, where it splits off.
In Guthrie, US-77 meets State Highway 33. It continues northbound to serve as the eastern terminus of State Highway 164 and turns eastward toward Perry. After passing the north end of State Highway 86, it turns back northward and has a half-interchange with the Cimarron Turnpike. It then carries State Highway 15 for four miles. At Tonkawa, it begins a wrong-way concurrency with U.S. Highway 177 and U.S. Highway 60. It splits off to the north to head through Ponca City and Newkirk, before crossing over the Kansas line towards Arkansas City, Kansas.
In addition, US-77 has a truck route through downtown Pauls Valley.