He was signed by the Miami Dolphins as an undrafted free agent in 2008. That same year, he was later cut after not making the final squad.

In the 2010 NFL season, he emerged as the starting fullback for the Oakland Raiders, hauling in 25 receptions for 333 yards and 3 touchdowns while rushing for 122 yards and one touchdown. He blocked for his teammate running back Darren McFadden, who rushed for 1,157 yards and 7 touchdowns.

In 2012, after a series of injuries to McFadden and back-up Mike Goodson, Marcel Reece was switched from fullback to running back. He rushed for a total of 271 yards and recorded 52 receptions for 496 yards and one touchdown.

In 2013, both McFadden and back-up Rashad Jennings were limited due to injures, allowing Reece to line up at running back. On December 27, 2013, he was the lone Raider selected for the 2013 Pro Bowl, his second Pro Bowl nomination.

On December 23, 2014, Reece was selected once again to the Pro Bowl, marking his third straight Pro Bowl appearance at the fullback position.

In 2015, after Derek Carr suffered an injury to his throwing hand, Matt McGloin stepped in at quarterback, finding Reece for two receiving touchdowns, in a season-opening loss to the Cincinnati Bengals. On December 22, 2015, he was selected to his fourth straight Pro Bowl. On December 28, 2015, Reece was suspended for four games for violating league policy on performance-enhancing substances.

Reece was released by the Raiders on September 26, 2016.

On December 6, 2016, Reece was signed by the Seattle Seahawks.

On July 28, 2017, Reece was re-signed by the Seahawks. He was released on September 2, 2017.

On September 11, 2020, the Las Vegas Raiders announced Reece’s return in an executive position, with the newly-created title of Senior Advisor to the Owner and President for Mark Davis and Marc Badain.