The New York Giants selected Rote with the first overall pick in the 1951 NFL Draft. He started out as a running back, but after the first two years switched to wide receiver due to a knee injury. When Rote retired after the 1961 season, he had become the Giants' career leader in pass receptions (300), receiving yardage (4,805), and touchdown receptions (48). He was second highest in total touchdowns (56) and fifth-leading scorer (312 points). His average gain per catch was 15.9 yards. In all, Rote played in four world championship games, including the 1956 NFL Championship Game against the Chicago Bears, and the 1958 game won by the Baltimore Colts in sudden-death overtime known as The Greatest Game, the first ever nationally televised NFL championship game. Rote was the captain of the New York Giants for eight years.