The series focusing on the adventures of Lois Lane began publication with a March/April 1958 cover date and ended its run in September/October 1974, with 137 regular issues and two 80-page Annuals.

[11] "The Monkey's Paw", a story from issue #42 (July 1963), featured a one-panel appearance, with his costume miscolored, by the defunct Fawcett Comics' Captain Marvel, who was not yet a DC character.

[17] The series saw the debut of the Silver Age heroine "Rose & The Thorn" in a backup feature that ran from #105 (October 1970)[18][19] through #130 (April 1973).

Editor E. Nelson Bridwell had several characters and plot concepts from Jack Kirby's "Fourth World" appear in issues #111–119 (July 1971 – February 1972).

[22] The release of the last issue of Superman's Girl Friend, Lois Lane was delayed for several months due to a nationwide paper shortage.