He spent his first two seasons with the Chicago Bears, who selected him seventh overall in the 1958 NFL draft, and played the remainder of his career for the Cowboys.

Howley was also named the MVP of Super Bowl V and is the only player on a losing team to receive the award.

Howley played guard and center during his three years at varsity, in which the Mountaineers compiled a 21–8–1 record, including a 21–7 victory over Penn State, West Virginia's last until 1984.

He played in the East-West Shrine Game and the Senior Bowl, which helped him get noticed by the Chicago Bears.

Howley was selected seventh overall in the 1958 NFL draft by the Chicago Bears, playing for two seasons before retiring after what appeared to be a career-ending knee injury he sustained in August 1959, at training camp in Rensselaer, Indiana.

[8] He returned to West Virginia that year to take a job running a filling station, planning to permanently retire from professional football.

At the conclusion of the 1963 season, Howley was named to The Sporting News All-East NFL team for the first time.

[12] The following season, Dallas made it back to Super Bowl VI, and Howley recorded a fumble recovery and a 41-yard interception in the Cowboys 24–3 win over the Miami Dolphins.

[14] Howley suffered a left knee injury from a crackback block by Charley Taylor in the win over rival Redskins late in the 1972 regular season.

[20] On February 9, 2023, Howley was elected to the Pro Football Hall of Fame[21] and was formally enshrined on August 5, with his son Scott delivering a speech on his behalf.

[23] In 1977, Howley founded Happy Hollow Ranch, a cattle and quarter horse operation near Wills Point, Texas.