Ingram was drafted by the Giants in the first round (28th overall) in the 1987 NFL Draft. He is probably best known for a third down play in Super Bowl XXV in which he eluded at least five Buffalo Bills defenders to achieve a critical first down for the Giants to sustain a long touchdown drive. He finished the game as the Giants top receiver with five catches for 77 yards. As a Miami Dolphin, in a game against the New York Jets, Ingram caught four touchdown passes from Dan Marino. The most notable was the game-winning touchdown, which was the result of Marino faking out the Jets defense by indicating he was going to spike the ball to stop the clock. Instead, he lobbed a short pass to Ingram, who was open in the end zone.
Ingram retired after the 1996 season.
On September 16, 2008, Ingram was sentenced to seven years in prison and up to five years of probation for money laundering and fraud. He was also ordered in a Long Island federal court to pay $252,000 in restitution. Ingram failed to show up to a federal prison in Ashland, Kentucky to turn himself in on December 5, 2008, and an arrest warrant was issued. On January 2, 2009, Ingram was arrested in a Flint, Michigan hotel room, where he was preparing to watch his son play in the 2009 Sugar Bowl. Alabama lost the game to the Utah Utes by a score of 31–17. On March 22, 2010, in a courtroom in Central Islip, New York, Ingram was sentenced to an additional two years in prison for jumping bail to see his son, Mark Ingram Jr. play for Alabama. He was housed at Yazoo City Federal Correctional Complex (FCC) as inmate 22749-050, and was then in the custody of the Residential Reentry Management Detroit. Ingram was released from prison in early 2015.
In 2008, Ingram's son, Mark Ingram Jr., began his college football career as a running back for the Alabama Crimson Tide, coached by Nick Saban, who coached Mark Sr. as an assistant at Michigan State. On December 12, 2009, Mark Jr. won the Heisman Trophy. On January 7, 2010 Alabama won the National BCS Championship, and Mark Jr. received honors as Offensive MVP.
On April 28, 2011 Mark Jr. was selected by the New Orleans Saints in the 1st Round (28th overall) of the 2011 NFL Draft, marking the first time a father and son were drafted with the same pick in the NFL Draft.