Unhappy being relegated to a reserve role under head coach Weeb Ewbank, Vessels retired after the 1956 season to take up the construction business in Coral Gables, Florida.

Billy Vessels gained prominence with the Oklahoma Sooners as a star of what was heralded as "The Phantom Backfield" together with All-American quarterback Eddie Crowder and fellow backs Buck McPhail and Buddy Leake.

Playing under the legendary Bud Wilkinson, he became the first of seven Sooners, followed by Steve Owens (1969), Billy Sims (1978), Jason White (2003), Sam Bradford (2008), Baker Mayfield (2017), and Kyler Murray (2018) to win the award.

Vessels played only one full season in Canada, seeing action for just one game with the Kitchener-Waterloo Dutchmen of the Ontario Rugby Football Union (ORFU) — who were acting as a farm team for Edmonton in 1954 — in an attempt to qualify as a non-import under rules governing at that time.

[5] Colts' Head Coach Weeb Ewbank saw Vessels as a promising addition to the team's offensive attack but was concerned about his chronic injury problems during the preseason: "We know he was a great football player in college.

"[6] Vessels made his eagerly anticipated NFL debut in the September 16 season opener against the Washington Redskins, joined by a rookie speedster out of Penn State, Lenny Moore.

In front of a home crowd of 28,471, the Colts defeated the Redskins by a score of 21–13, but it was Lenny Moore who particularly shined, seemingly consigning Vessels to a backup role.

[7] Owing to the crowded Colts backfield, coach Ewbank moved the halfback Vessels to the flanker back position, forerunner of the modern wide receiver.

Vessels was unhappy with his role as a reserve running back under Weeb Ewbank and decided to retire from football after the 1956 season, returning home to Florida to take up the construction business.