He played college football for the Texas Longhorns before being selected by the Pittsburgh Steelers with the third overall pick of the 1948 NFL draft and traded to the Chicago Bears.

Layne's two sisters stayed with his mother while he was sent to Fort Worth to live with his aunt and uncle, Mimi and Wade Hampton.

[2][3][4] One of the most successful quarterbacks ever to play for Texas, Layne was selected to four straight All-Southwest Conference teams from 1944 to 1947, and was a consensus All-American in his senior year.

[10] In 1947, Blair Cherry replaced Dana X. Bible as head coach at Texas and he decided to install the T-formation offense.

The change was a success, as Layne led the Southwest Conference in passing yards, made the All-Conference and All-American teams, and finished sixth in Heisman Trophy voting to John Lujack of Notre Dame.

[12] Layne engineered a fourth-quarter touchdown drive that would have tied the game, but kicker Frank Guess pushed the extra point wide and the Longhorns lost 14–13.

[13] They fell to eighth, and finished behind SMU in the Southwest Conference, but gained an invitation to the Sugar Bowl, where Layne and the Longhorns beat number-six Alabama.

As a result of his 10-of-24, 183-yard performance, Layne won the inaugural Miller-Digby award presented to the game's most valuable player.

He won his first career start, in 1944, when he was managed by his future football coach Blair Cherry, versus Southwestern, 14–1, in a complete-game, 15-strikeout performance.

[2] He went 6–5 with a 7.29 ERA, and had bids from the New York Giants, the Boston Red Sox, and the St. Louis Cardinals to join their staffs, but he preferred to go to the National Football League, where he could play immediately rather than grind out several years in the minor-league system.

Layne did not want to play for the Steelers, the last team in the NFL to use the single-wing formation, so his rights were quickly traded to the Chicago Bears.

[20] He was offered $77,000 to play for the Colts, but George Halas, who attended the Sugar Bowl victory over Alabama and sat with Cherry and Layne after the game, "sweet talked" him into signing with the Bears.

[22] For the next five years, Layne was reunited with his great friend and Highland Park High School teammate Doak Walker, and together they helped make Detroit into a champion.

They fell short of a three-peat in 1954 when they lost 56–10 to Cleveland Browns in the NFL championship game, a loss which Layne explained by saying, "I slept too much last night.

[24] His replacement, Tobin Rote, finished the season and led the Lions to victory in the championship game in Detroit, a 59–14 rout of the Cleveland Browns.

[26][27][28] During his eight seasons in Detroit, the Lions won three NFL championships and Layne played in four Pro Bowls, made first-team All-Pro twice, and at various times led the league in over a dozen single-season statistical categories.

Later he stated that the biggest disappointment in his football career was having never won a championship for the Pittsburgh Steelers and specifically, Art Rooney.

[20] By the time Layne retired before the 1963 season, he owned the NFL records for passing attempts (3,700), completions (1,814), touchdowns (196), yards (26,768), and interceptions (243).

[37] After retirement, Layne spent 24 years as a businessman back in Texas in Lubbock, working with his old college coach, Blair Cherry.

That line was later used by baseball player Mickey Mantle, a Dallas neighbor and friend of Layne's, who also died in part due to decades of excess alcohol consumption.

"[31] In 1958, the defending NFL champion Lions traded Layne to the Pittsburgh Steelers in early October for Earl Morrall and two draft choices.

"[41] While this story has been called a hoax, particularly because the quote was never published at the time,[42] over the next half-century after this trade, the Lions had the sixth lowest winning percentage of any team in the NFL.

The Lions have had multiple consecutive losing seasons and have been swept by division rivals constantly, and are 3–14 in postseason appearances since their 1957 championship, the worst record of any team; their three playoff wins were over Dallas in 1991, and Los Angeles and Tampa Bay in 2023.

[44] In the 2009 NFL draft, immediately after the supposed curse had expired, the Detroit Lions selected University of Georgia quarterback Matthew Stafford first overall.

[45] In 2011, Stafford's first full injury-free season, he led the Lions to their first playoff berth since 1999, but lost to Drew Brees and the New Orleans Saints.

[51] After starting their 2022 season 1–6, the Lions performance notably improved after the episode aired; they won eight of their remaining ten games to end with a winning record, prompting speculation that Manning may have succeeded in lifting the curse.

[55] As of the end of the 2024 regular season the Lions have a record of 34 wins and 10 losses (including playoffs) since the incantation was performed by Daniels and Manning at Ford Field.