It runs north from U.S. Route 101 in Ventura through the Transverse Ranges and the western side of the San Joaquin Valley to Interstate 5 at a point east of Tracy.

SR 33 then continues north as Maricopa Highway, an undivided surface road, through Ojai, following Matilija Canyon past the easternmost extremity of the Santa Ynez Mountains in Los Padres National Forest, and passing over the Transverse Ranges at Pine Mountain Summit.

Between Taft and Avenal it roughly parallels Interstate 5 and the eastern foothills of the Temblor and Diablo ranges; for the first 15 miles (24 km) of the portion following the axis of the Midway-Sunset Oil Field.

It departs again west of Los Banos, turning north to Santa Nella (where it has an interchange with I-5), and roughly parallels I-5 and the San Joaquin River until its northern terminus at I-5 and Bird Road southeast of Tracy.

In the portions of the route in Kern and Fresno Counties, SR 33 passes through one of the United States' largest petroleum extraction fields, with hundreds of nodding oil pumps along the highway.

Except where prefixed with a letter, postmiles were measured on the road as it was in 1964, based on the alignment that existed at the time, and do not necessarily reflect current mileage.