It goes from State Route 210 in La Verne east to Interstate 215 in San Bernardino, passing through Claremont, Upland, Rancho Cucamonga, Fontana and Rialto along Foothill Boulevard.

Foothill Boulevard continues east through Rancho Cucamonga through an interchange with I-15 before entering Fontana, and passing well north of the California Speedway.

SR 66 continues east into San Bernardino, before curving to the north as 5th Street and terminating at I-215 south of downtown.

[8] By 2013, the portion from east of Pomona to the eastern boundary of Rialto had been relinquished to the various cities that the route passed through.

[9] 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.