Lloyd was born in Beresford, South Dakota, and after graduating from Yankton College in 1940 started his career with a number of local radio stations around the Midwest. He served in the U.S. Marine Corps during World War II.
During the 1950s, Lloyd was the sidekick to Jack Brickhouse on Cubs and Chicago White Sox television broadcasts, during a time when WGN-TV covered both teams' home games and selected road games. When Cubs radio play-by-play man Jack Quinlan died in an auto accident during spring training, in 1965, Lloyd was promoted to that position and Lloyd Pettit was brought in to back up Brickhouse.
Various announcers have punctuated particularly exciting moments during a game with the exclamation "Holy..." something: Harry Caray and Phil Rizzuto invoked "Holy cow!" Milo Hamilton's was "Holy Toledo!" For a while, Lloyd was known for "Holy mackerel!" During the 1970s, a fan sent the broadcasting team a cowbell, and when a Cubs player would hit a home run, Lloyd and Boudreau would ring the bell as Lloyd proclaimed, "It's a bell-ringer!"
Vince Lloyd was also the first baseball announcer to interview a current US President on TV, when he spoke to John F. Kennedy during the White Sox TV pre-game show for the traditional Washington, D.C. season opener, at Griffith Stadium on April 10, 1961.