During his career, he mainly wrestled for Empresa Mundial de Lucha Libre in Mexico where he won the Mexican National Light Heavyweight Championship, Mexican National Middleweight Championship, Mexican National Tag Team Championship with Rayo de Jalisco, Mexican National Welterweight Championship, NWA World Middleweight Championship and the NWA World Welterweight Championship. He is said to have popularized professional wrestling in Mexico just as Rikidōzan did in Japan or like Hulk Hogan did in the United States. Guzmán's son followed him into wrestling as El Hijo del Santo, or the Son of Santo. In 2018, WWE inducted him into their Hall of Fame in the Legacy category.