He played seven seasons as an offensive and defensive tackle in the National Football League (NFL) during the 1950s for the Cleveland Browns and the Green Bay Packers before starting a 36-year career as an assistant coach.

Sandusky played six seasons for the Browns, who won NFL championships in 1950, 1954 and 1955 behind an offense that featured quarterback Otto Graham and end Dante Lavelli.

Led by quarterback Johnny Unitas, the Colts won an NFL championship in 1959 and beat the Dallas Cowboys to win Super Bowl V in 1970.

[6] Led by a strong defense and an offense that featured quarterback Otto Graham and end Dante Lavelli, the Browns advanced to the NFL championship in each of Sandusky's six seasons with the team.

[9] Cleveland coach Paul Brown traded Sandusky along with halfback Chet Lyssy to the Green Bay Packers in August 1956 for a late-round draft pick in 1957.

[12] He stayed there until 1959, when he was hired by Baltimore Colts head coach Weeb Ewbank, who had been an assistant with the Browns when Sandusky played in Cleveland.

[12] He was initially the defensive line coach for the Colts, who finished Sandusky's first season with a 9–3 win–loss record and won the NFL West behind an offense led by quarterback Johnny Unitas and halfback Lenny Moore.

[12] The Colts finished with an 11–2–1 win–loss–tie record in 1970 and beat the Dallas Cowboys to win Super Bowl V.[20] The team reached the conference championship game the following year, but faltered at the beginning of the 1972 season.

[21][22] After starting with a 1–4 record, Baltimore general manager Joe Thomas fired McCafferty in October, saying the team was going to replenish its roster with younger players.

[23] At Thomas's urging, Sandusky immediately benched Unitas and replaced him with Marty Domres, a quarterback acquired from the San Diego Chargers in a preseason trade.

[30] He was offered a job as director of pro personnel for the Colts before the team moved to Indianapolis in 1984, but he declined it, saying he wanted to stay near his family in Florida.

Long-time New York Giants general manager Ernie Accorsi once called him "the greatest coach in the history of the league that never got a chance".