[2] Foothill Boulevard starts off in Newhall Pass in the Sylmar district of the city of Los Angeles at Sierra Highway near the southern terminus of the Antelope Valley Freeway (SR 14).

The western segment of Foothill Boulevard ends at Oak Grove Drive in Pasadena, where it heads southeast across the unsigned freeway alignment, with an interchange at Yucca Lane.

The city of Pasadena and the County of Los Angeles both agreed to change the name of the spur north of Foothill to Altadena Drive; Santa Anita Avenue between Foothill and the southern city limit of Pasadena was also renamed Altadena Drive, though that name change did not occur until the early 1970s.

Before Huntington Drive was built through Duarte, Foothill Boulevard ran along the current routing of Royal Oaks Drive between Shamrock Avenue in Monrovia just past Highland Avenue in Duarte, meeting the current end of Foothill Boulevard at the San Gabriel River bridge.

[citation needed] The third section of Foothill Boulevard is accessed by going south on Mountain and going east on Huntington Drive through the Los Angeles County cities of Monrovia and Duarte.

At the interchange with SR 210 near the San Dimas/La Verne city limits, Foothill Boulevard is defined as State Route 66, although it is unsigned in Los Angeles County.

[citation needed] Foothill Blvd (SR 66) passes through the north end of Pomona and Claremont before entering San Bernardino County in the city of Upland.

Foothill Boulevard continues east through the cities of Fontana (and such landmarks as Bono's Restaurant and Deli), Rialto, and San Bernardino.

At the interchange with Interstate 215, the SR 66 designation ends (at downtown San Bernardino), although old US 66 headed north on Mount Vernon Avenue (along old US 395/US 91) before exiting the Inland Empire over the Cajon Pass.