Fine became particularly prominent as a cover artist. Fine, along with "Plastic Man" creator Jack Cole, was a ghost-artist on Will Eisner's celebrated Sunday-supplement newspaper comic book "The Spirit" during Eisner's World War II military service, Fine inking over Cole's pencil work. Some of these were reprinted in Quality's "Police Comics" and "The Spirit" comic book, where Fine's work continued to appear through 1949, five years after Fine had left comics. Joe Simon, an artist and the first editor of Marvel Comics, called Fine his "favorite artist... He was also Jack Kirby's favorite artist. I know that Jack was a fan of and greatly influenced by Fine’s work". Leaving comic books in 1944, Fine segued into newspapers by drawing Sunday advertising comics. Starting out at Johnstone and Cushing, he formed his own company with Don Komisarov, whom he had met doing "The Throp Family" for "Liberty" in 1946. He had many accounts, but his two most enduring were the series he did for Philip Morris USA and the Sam Spade strip for Wildroot Cream-Oil. He later drew the comic strips "Taylor Woe" (1949), "Adam Ames" (1959) and "Peter Scratch" (1965). In a single return to comic books, he contributed to a toy company's custom one-shot, "Wham-O Giant Comics" (1967), illustrating a two-page story, "The Man From Aeons", starring a prehistoric man who, though named "Tor", was not the same-name caveman character created in the 1950s by Joe Kubert. Fine also worked on the strip "Space Conquerors" in the magazine "Boys' Life" from the late 1960s until his death. He and writer Gill Fox, whom he had met during his time with Eisner & Iger and remained in contact with, were developing new comic strips when Fine was found dead of a heart attack in his studio. By the late 1960s, Fine lived in Lido Beach, New York, on Long Island, owning two houses there. Fine's "Spirit" work has been reprinted in DC Comics' hardcover collections "The Spirit Archives" vols. 5 to 9 (2001–2003), spanning July 1942 to December 1944. Selections of Fine's other comics works, including the Flame, Doll Man, Uncle Sam, the Ray, and Black Condor, have been reprinted in Pure Imagination's "Lou Fine Reader", by Greg Theakston, vols. 1 (2003, ) and 2.