Lazzeri was born and raised in San Francisco, California. He dropped out of school to work with his father as a boilermaker, but at the age of 18, began to play baseball professionally. After playing in minor league baseball from 1922 through 1925, Lazzeri joined the Yankees in 1926. He was a member of the original American League All-Star team in 1933. He was nicknamed "Poosh 'Em Up" by Italian-speaking fans, from a mistranslation of an Italian phrase meaning to "hit it out" (hit a home run).