Van Looy was active on the cycling circuit between the 1950s and 1960s, and went down in history as the first to win all five one-day classics (Milan–San Remo, Tour of Flanders, Paris–Roubert, Liège–Bastogne–Liège and Giro d’Italia). Only his compatriots Eddy Merckx and Roger De Vlaminck can boast of that achievement.

Throughout his career, Van Looy won 37 stages of the biggest competitions (Tour de France, Giro d’Italia, Vuelta), and his gold medals at the 1952 Olympic Games in Helsinki and the world championships in 1960 and 1961.

In total, he managed to reach 371 victories in his professional career.