In the 1972 NFL draft he was chosen by the Pittsburgh Steelers in the first round, the 13th selection overall. His selection by the team was considered controversial at the time, as many thought the team would select his Penn State teammate, Lydell Mitchell. (Mitchell was later selected by the Baltimore Colts in the draft.) He played his first 12 years in the NFL with the Steelers; his 13th and final year (1984) was spent with the Seattle Seahawks. He was inducted into the Pro Football Hall of Fame in 1990.
Harris was chosen for 9 consecutive Pro Bowls from 1972 through 1980, and was All-Pro in 1977. He broke Jim Brown's record by rushing for more than 1,000 yards in 8 seasons. The tandem running package of Harris and Rocky Bleier combined with a strong defense to win four Super Bowls in the 1974, 1975, 1978, and 1979 seasons. In 1975 he was the Most Valuable Player of Super Bowl IX; in that game he rushed for 158 yards and a touchdown on 34 carries for a 16-6 win over the Minnesota Vikings. Harris was the first African American as well as the first Italian-American to be named Super Bowl MVP. Harris was a major contributor for the Steelers in all of their first four Super Bowl wins. His Super Bowl career totals of 101 carries for 354 yards are records and his 4 career rushing touchdowns are tied for the second most in Super Bowl history.
Critics complained about Harris' tendency to run out of bounds instead of taking on tacklers for extra yards. Harris felt that he extended his career by avoiding unnecessary contact.
In his 13 professional seasons, Harris gained 12,120 yards on 2,949 carries, a 4.1 yards per carry average, and scored 91 rushing touchdowns. He caught 307 passes for 2,287 yards (2091 m), a 7.4 average, and 9 touchdowns. While the Steelers no longer officially retire uniform numbers, they have not reissued his number 32 since he left the team, and it is generally understood that no Steeler will ever wear that number again.
Following the 1983 season, Harris and Walter Payton were both closing in on Jim Brown's NFL rushing record, and had asked the Rooney family for a pay raise. The Rooney family refused, and Harris threatened to hold out. The Steelers released Harris in training camp in 1984, which would start similar patterns years later with Rod Woodson and Alan Faneca both asking similar demands before leaving in free agency. (Free agency, as it is seen today in the NFL, was not existent at the time of Harris's release.) Harris would sign with the Seattle Seahawks during the 1984 season and would play eight games with the team, earning a few hundred yards before retiring.
Harris was a key player in one of professional football's most famous plays, dubbed "The Immaculate Reception" by Pittsburgh sportscaster Myron Cope. In a 1972 playoff game, the Oakland Raiders were leading the Steelers 7-6 with 22 seconds to play when a Terry Bradshaw pass was deflected away from intended receiver John "Frenchy" Fuqua right as defender Jack Tatum arrived to tackle Fuqua. Harris snatched the ball just before it hit the ground and ran it in to win the game. The Raiders challenged the touchdown, claiming that Fuqua had handled the ball before Harris, which would invalidate the score because at that time it was against the rules for two offensive receivers to touch the ball. The Steelers maintained that the ball had touched Tatum instead. According to a recounting by the Pro Football Hall of Fame, the film of the play is inconclusive. (Later controversy stemming from Raiders linebacker Phil Villapiano's assertion that Harris was only in position to catch the ball because he was lazy is widely discounted. Harris's original assignment on the play was to block, but he headed downfield when the Raiders forced Bradshaw out of the pocket, and can be clearly seen running before catching the deflected ball.)
In 1999, he was ranked number 83 on The Sporting News' list of the 100 Greatest Football Players.
In 2006, The Heinz History Center, home of the Western Pennsylvania Sports Museum, installed a life-size figure of Harris in the grand concourse of Pittsburgh International Airport. The statue is a recreation of Harris' "Immaculate Reception."
He is also a paid representative for the Harrah's/Forest City Enterprises casino plan for downtown Pittsburgh. This association has earned him the tongue-in-cheek nickname "Franco Harrahs".
On 07/09/06, Franco Harris made a celebrity appearance in the 2006 Taco Bell All-Star Legends and Celebrity Softball Game at PNC Park in Pittsburgh.
In August, 2008, Harris attended the Democratic National Committee Convention in Denver, Colorado as part of the Pennsylvania delegation.