Van Cleef's natural acting talent got him noticed by famed director Stanley Kramer. He cast the young actor as the villainous Jack Colby in High Noon (1952). His success in this role and other westerns typecast him; throughout the 1950s, Van Cleef usually portrayed the bad guy.
Throughout the 1960s and 1970s, Van Cleef worked steadily in Europe. When the spaghetti western craze died down, he returned to Hollywood, remarried once more, and continued acting in films, mostly low-budget affairs. At the age of 59, Van Cleef took the starring role in the short-lived NBC series The Master, which was canceled after just 13 episodes.