Alexander was drafted by the San Francisco 49ers with the eighth pick in the first round of the 1963 NFL Draft. He was also drafted by the Denver Broncos of the American Football League with the fifth overall pick, but chose to sign with San Francisco. Alexander played alongside Pro Football Hall of Fame cornerback Jimmy Johnson. Alexander was selected to play in the Pro Bowl in 1968, after a season in which he had a career-high nine interceptions, including an interception he returned 66 yards for a touchdown.