And yet, to many people he will always be the lovable dad from the 1980s sitcom "Webster" or the big cowboy who famously punched out a horse in "Blazing Saddles."
The rugged player, who anchored the Detroit Lions' defense and then made a successful transition to an acting career, with a stint along the way as a commentator on "Monday Night Football," died Wednesday. He was 77.
Karras had recently suffered kidney failure and been diagnosed with dementia. The Lions also said he had suffered from heart disease and, for the last two years, stomach cancer. He died at home in Los Angeles surrounded by family members, said Craig Mitnick, Karras' attorney.
"Perhaps no player in Lions history attained as much success and notoriety for what he did after his playing days as did Alex," Lions president Tom Lewand said.
His death also will be tied to the NFL's conflict with former players over concussions. Karras in April joined the more than 3,500 football veterans suing the league for not protecting them better from head injuries, immediately becoming one of the best-known names in the legal fight. Mitnick said the family had not yet decided whether to donate Karras' brain for study, as other families have done.
Born in Gary, Ind., Karras starred for four years at Iowa. Detroit drafted Karras with the 10th overall pick in 1958 and he was a four-time All-Pro defensive tackle over 12 seasons with the franchise.
He was the heart of the Lions' famed "Fearsome Foursome," terrorizing quarterbacks for years. The Lions handed the powerful 1962 Green Bay Packers their only defeat that season, a 26-14 upset on Thanksgiving during which they harassed quarterback Bart Starr constantly.
Packers guard Jerry Kramer wrote in his diary of the 1967 season about his trepidation over having to play Karras.
"I'm thinking about him every minute," Kramer wrote.
For all his prowess on the field, Karras may have gained more fame when he turned to acting in the movies and on television.
Playing a not-so-bright bruiser in Mel Brooks' "Blazing Saddles," he not only slugged a horse but also delivered the classic line: "Mongo only pawn in game of life."
Several years before that, Karras had already become a bit of a celebrity through George Plimpton's behind-the-scenes book about what it was like to be an NFL player in the Motor City, "Paper Lion: Confessions of a Second-string Quarterback."
That led to Karras playing himself alongside Alan Alda in the successful movie adaption - Karras and Plimpton remained friends for life and one of Karras' sons is named after Plimpton - and it opened doors for Karras to be an analyst alongside Howard Cosell and Frank Gifford on "Monday Night Football."
In the 1980s, he played a sheriff in the comedy "Porky's" and became a hit on the small screen as Emmanuel Lewis' adoptive father, George Papadapolis, in the sitcom "Webster."
He also had roles in "Against All Odds" and "Victor/Victoria." He portrayed George Zaharias in CBS's "Babe," in which he starred with Susan Clark, who later became his wife. The two formed their own production company and it was Clark who played the role of his wife on "Webster."
Recently, his wife said Karras' quality of life has deteriorated because of head injuries sustained during his playing career.
Susan Clark said her husband couldn't drive after loving to get behind the wheel and couldn't remember recipes for some of the favorite Italian and Greek dishes he used to cook.
"This physical beating that he took as a football player has impacted his life, and therefore it has impacted his family life," Clark told The Associated Press earlier this year. "He is interested in making the game of football safer and hoping that other families of retired players will have a healthier and happier retirement."
Clark has said he was formally diagnosed with dementia several years ago and has had symptoms for more than a dozen years. He joined hundreds of other former players suing the league.
"It's the same thing as back in the gladiator days when the gladiators fought to death," Mitnick, who represents Karras and hundreds of others in the suit, has said. "Fans care about these guys when they're playing and they are heroes. But as soon as you're not a hero and not playing the fan doesn't really care what happens to them."
The NFL has said it did not intentionally seek to mislead players and has taken action to better protect players and to advance the science of concussion management and treatment.
Karras played his entire NFL career with the Lions before retiring in 1970 at age 35. He was a first-team All-Pro in 1960, 1961 and 1965, and he made the Pro Bowl four times. He missed the 1963 season when he was suspended by NFL Commissioner Pete Rozelle in a gambling probe. Karras was recognized by the Pro Football Hall of Fame as a defensive tackle on the All-Decade Team of the 1960s.
Karras later wrote an autobiography, "Even Big Guys Cry," and two other books, "Alex Karras' and "Tuesday Night Football." Lewand said Karras also loved to garden and cook.
"We know Alex first and foremost as one of the cornerstones to our 'Fearsome Foursome' defensive line of the 1960s and also as one of the greatest defensive linemen to ever play in the NFL," Lewand said. "Many others across the country came to know Alex as an accomplished actor and as an announcer during the early years of 'Monday Night Football.'"___
AP Sports Columnist Tim Dahlberg and AP Pro Football Writer Howard Fendrich contributed to this report.