Lööf studied at the Stockholm Art Academy in the early 1960s. In 1967, he started his most famous comic strip Felix, which soon gained popularity into many parts of the world. Mixing humor and adventure, Felix has sometimes been described as a more naivistic version of The Adventures of Tintin. Later, Lööf created other comics, such as Bellman (a humor strip about a Stockholm hobo) and Ville (a "comedic adventure" about an unemployed Stockholm author, teaming up with Olof Palme and Carl XVI Gustaf to fight the bad guys).
In the early 1970s, Lööf participated as actor in a few productions, among them the Swedish cult children's TV show Tårtan (The cake) about three incompetent and filthy sailors-turned-bakers. In 1985, Lööf produced his own children's show, the animated Skrot-Nisse och Hans Vänner (Scrap-Nils and his friends), for Swedish National Television.
Jan Lööf's own books for children have been very popular, both in Sweden and worldwide. Among them are The Story of the Red Apple and Uncle Louie's Fantastic Sea Voyage. He has also illustrated children's books written by his friend and colleague Carl-Johan de Geer.
Lööf is known to spend his spare time playing the saxophone.