The sixth-generation F-Series was introduced in 1973. This version of the F-Series continued to be built on the 1965 fourth-generation's revised platform, but with significant modernization and refinements, including front disc brakes, increased cabin dimensions, full double-wall bed construction, and increased use of galvanized steel.

The FE engine series was discontinued in 1976 after a nearly 20-year run, replaced by the more modern 335 and 385 series engines. In 1975, the F-150 was introduced in between the F-100 and the F-250 to avoid certain emission control restrictions. For 1978, square headlights replaced the previous models' round ones on higher-trim-package models, such as Lariat and Ranger, and became standard equipment for 1979. Also for 1978, the Ford Bronco was redesigned into a variant of the F-Series pickup; 1979 was the last year that the 460 engine was available in a half-ton truck.