Karras was born in Gary, Indiana, the son of Dr. George Karras, a Greek immigrant (from Chios) who graduated from the University of Chicago and got his medical degree in Canada. There, George Karras met and married a Canadian woman, Alex’s mother, Emmeline (née Wilson), a registered nurse. George Karras opened a medical practice in Gary, but he died when Alex was thirteen years old. By that time, Alex Karras had learned to play football in a parking lot near his home, and he blossomed into a four-time Indiana all-state selection at Gary Emerson High School.

His older brothers, Lou (a future member of the Redskins) and Ted (who later played with the Bears and Lions), had played at Purdue but later Ted transferred to Indiana. Because of this, Alex said, “Indiana had the inside track” on recruiting him, but shortly after he graduated from high school, several coaches from the University of Iowa took Karras to secluded Spencer, Iowa, to keep him away from rival recruiters. There they persuaded him to sign with the Hawkeyes.

Karras struggled his first few years at Iowa, with classwork, homesickness and with his coach, Forest Evashevski. He was a pledge at Sigma Nu fraternity during his first year in school. Alex probably would have left Iowa had he not befriended a Greek theater owner, as well as fellow players Cal Jones and Bob Commings. Karras’ sophomore year with Iowa in 1955 got off to a rocky start when he showed up for practice twenty pounds overweight. Karras was also hampered that season by a cracked ankle bone. After being disappointed at not getting to play in the season finale, Karras threw a shoe at Evashevski and quit the team. Karras did not earn a football letter for the 1955 season.

Karras went to summer classes and later rejoined the football team, but a strained relationship resurfaced. Evashevski promised to start Alex Karras in the 1956 season opener against Indiana, when Alex would square off against his brother, Ted. But Evy played Karras off the bench instead, and Karras quit the team again. This time, he agreed to rejoin the team only after making Evashevski promise he would not talk to Karras other than in a purely coaching capacity. (Evashevski always denied any special agreement with Karras.) Iowa took the lead in the 1956 Big Ten title race with a 7-0 victory over Minnesota. The Hawkeyes then clinched the Big Ten title and Iowa’s first ever Rose Bowl berth by defeating Ohio State, 6-0. Karras sealed the game with a quarterback sack on the game’s final play.

Iowa’s final regular season game in 1956 was against Notre Dame, which Iowa won, 48-8. Karras called it his biggest college win, saying, “The Karrases have always had a rivalry with Notre Dame. The school was just 60 miles down the road from our home and we wanted to beat ’em at anything.” However, after the game, Karras got into a physical battle with Evashevski. Karras did not enjoy his trip to the Rose Bowl, either. “Pasadena was the most boring town I’ve ever been in,” said Karras. Karras helped the Hawkeyes win the 1957 Rose Bowl over Oregon State, 35-19. He was a first team All-American in 1956.

Karras spent the summer of 1957 with an American track team of Greek descent. He participated in the shot put, throwing a respectable 52 feet. In his senior season, Alex Karras was the most dominant lineman in the nation, winning the 1957 Outland Trophy. He also was the runner-up in the voting for the Heisman Trophy. Karras and Ohio State tackle John Hicks (in 1973) are two of only three linemen ever finishing so high in the Heisman Trophy voting. In 1949, Leon Hart, a Notre Dame end became the only lineman ever to win the Heisman Trophy.

Karras was drafted in the first round of the NFL draft by the Detroit Lions in 1958. He quickly became one of the dominant defensive tackles in the NFL, playing for 12 seasons (1958-1962, 1964-1970) with the same team, but missing the 1963 season for gambling activities. From 1960 to 1966, except for 1963, he played next to Roger Brown, a formidable pair of defensive tackles, until the latter was traded to the Los Angeles Rams. From 1958 to 1970, the Lions were over .500 six of the 13 years, making the playoffs only once, 1970, with a 10-4 win-loss record, Karras’ final year. Aside from 1970, their best years were 1962 (11-3) and 1969 (9-4-1). In 1962, the Lion defense allowed 177 points (12.6 points/game), in 1969 188 points (13.4 points/game), and in 1970 202 points (14.4 points/game), for all three years the second-least in the NFL, thanks in large part to a tough and rugged defensive line led by Karras. Despite not allowing a touchdown in the divisional round of the 1970-71 NFL playoffs, the Lions lost to the Dallas Cowboys 5-0, his first playoff game and his final game.

Karras was called an “iron man” since he missed only one game due to injury in his 12 NFL seasons and his 161 games played are the 15th most in Lions history. He made the Pro Bowl four times, and the Hall of Fame named him a member of the 1960s All-Decade team.

Before his NFL career got under way, Karras signed a contract as a professional wrestler on December 13, 1957, earning $25,000 during the six-month off-season. Eight days later, he officially signed with the Lions, spurning an offer from the Canadian Football League’s Winnipeg Blue Bombers. On January 7, 1963, Karras’s ownership in Detroit’s Lindell AC Bar became a source of controversy when league officials urged him to sell his financial interests in the place because of reports of gambling and organized crime influence. After first threatening to retire rather than give it up, Karras admitted placing bets on NFL games and was suspended by the league, along with Green Bay Packers’ running back Paul Hornung, for one season (1963).

During his exile, Karras returned to pro wrestling, taking on such memorable characters as Dick the Bruiser, but was then reinstated, along with Hornung, on March 16, 1964 by NFL commissioner Pete Rozelle. Upon returning to action in 1964, Karras once refused when an official asked him to call the pregame coin toss. “I’m sorry, sir,” Karras replied. “I’m not permitted to gamble.” During his first year back, player discontent with head coach George Wilson resulted in Karras asking to be traded. However, the Lions settled the issue when they fired Wilson after the 1964 NFL season.

After another season of controversy under new head coach Harry Gilmer, Karras was rumored to be ready to play out his option and sign with the expansion Miami Dolphins of the American Football League under his former coach Wilson. Instead, Karras signed a seven-year contract with the Lions on May 20, 1966, with Wilson stating that Karras had used the threat of signing with Miami to garner the large deal with Detroit. Despite the new contract, controversy remained, as Karras and Gilmer sparred in midseason, with the coach reportedly ready to release the veteran defensive tackle. As before, it would be the coach who would depart, with Karras’s former teammate Joe Schmidt taking over. On June 4, 1967, Karras once again hinted he would retire to work at a new business venture; once training camp began, though, Karras was back with the Lions. During that preseason, he jokingly commented that he would walk back from Denver if the AFL Broncos defeated the Lions. When that actually happened, Karras backtracked and flew home on the team plane. He was still an All-Pro selection in 1967 to 1969, but after sustaining a knee injury late in the 1970 season, reported to training camp in 1971 with his job in jeopardy. After unimpressive performances in the 1971 preseason, Karras was released, ending his playing career at age 35.

In 1968, he made his film debut playing himself in the film adaptation of George Plimpton’s nonfiction sports book Paper Lion.  Following his release by the Lions in 1971 – his appearances on The Tonight Show Starring Johnny Carson and a bit part in “The Mary Tyler Moore” show, the farewell party scene where Rhoda moves back to New York (1972) – he began acting on a full-time basis, playing a Tennessee boy turned Olympic weightlifter named Hugh Ray Feather in 1973’s The 500-Pound Jerk. He played a hulking villain who menaced Clint Walker in the ABC TV film Hardcase. A minor but memorable role came one year later in the western parody Blazing Saddles (1974): the very strong and slow-witted thug Mongo, who rode into town on a huge brahman (marked with “yes” and “no” passing signals), knocked out a horse with one punch, and famously responded to a question from Sheriff Bart with, “Don’t know…” (looking straight into the camera) “…Mongo only pawn in game of life.” That same year, he was quickly brought in by ABC to replace Fred Williamson as a commentator for the network’s Monday Night Football. He served three years in that role until leaving after the 1976 NFL season, with his most memorable comment coming in his first game, when he joked that bald Oakland Raiders’ lineman Otis Sistrunk, who never attended college, was from “the University of Mars”.  In 1972, Karras hosted a local weekly football program for Windsor, Ontario CBC affiliate CKLW-TV, The Alex Karras Football Show; his program generally preceded the CBC’s Wednesday night CFL telecasts.

Karras returned to acting with roles that included playing Sheriff Wallace in Porky’s (in which his wife, Susan Clark, also starred), and as western settler Hans Brumbaugh in Centennial. He played James Garner’s closeted gay bodyguard in the 1982 Blake Edwards’ film Victor Victoria. Karras played a darker role as Hank Sully, the right-hand-man of villain Jake Wise (played by James Woods) in the 1984 film, Against All Odds.  His television appearances included guest roles on M*A*S*H in the episode “Springtime”, The Odd Couple and a brief run on Match Game ’75. He also signed on to play the character “Super Jock” in commercials for a line of sports action toys by that name, produced by Schaper (1975). In 1977 he was cast in the lead of the TV movie Mad Bull.

In 1979 he had the role of Hans “Potato” Brumbaugh, a potato farmer, on the TV miniseries Centennial. He was known for his humorous endorsement of La-Z-Boy recliners, in an ad campaign which also featured NFL greats such as Miami Dolphins Coach Don Shula, and New York Jets legend Joe Namath. In the 1980s, Karras had memorable success in the TV sitcom Webster, playing George Papadapolis, the title character’s adoptive father, in a role that showcased his softer side. His real-life wife, Susan Clark, played his fictional wife in the series; Karras and Clark produced the series through their Georgian Bay Entertainment production company. The two met in 1975 while filming the made-for-television biopic Babe for CBS.

In his later years, Karras suffered several serious health problems, including dementia, heart disease, and cancer.  Karras was among 3,500 former NFL players to have filed lawsuits against the NFL in early 2012, over the long-term damage caused by concussions and repeated hits to the head.  On October 8, 2012, it was revealed by friend Tom McInerney that Karras had suffered from kidney failure; doctors gave him a few days to live. Karras was treated at the Saint John’s Health Center in Santa Monica, California, before being released into hospice care. After returning to his Los Angeles home with family, Karras died in the morning hours of October 10 from complications caused by kidney failure.