What is the record for most home runs in one game? October 13, 2022October 13, 2022Baseball History The record for most home runs in a game is four, held by 12 players. They are Bobby Lowe, Ed Delahanty, Chuck Klein, Gil Hodges, Joe Adcock, Willie Mays, Mike Schmidt, Bob Horner, Mark Whiten, Lou Gehrig, Pat Seerey, and Rocky Colavito.