In January 2018, Guice announced that he would forego his senior year at LSU in favor of the 2018 NFL Draft.
Guice attended LSU's pro day in April 2018, but opted to stand on his combine numbers and only performed positional drills.
At the conclusion of the pre-draft process, Guice was projected to be a first or second round pick by NFL draft experts and scouts.
He was ranked among the best running backs of the 2018 class, 
Predicted as a first round pick before the draft, Guice reportedly had his draft stock fall due to questions about his character and other incidents during the drafting process, such as an alleged verbal altercation between himself and Howie Roseman, executive of the Philadelphia Eagles.
Roseman and other Eagles personnel denied it took place, with Guice stating that the incident, as well as other rumors of him being lazy, immature, and dishonest, were not true.
Another issue allegedly occurred at the NFL Combine, where Guice claimed that he was asked if he liked men during an interview with a team, as well as if his mother "sells herself".
The NFL later investigated the claims, but found no proof it had happened.
Guice was eventually drafted in the second round, 59th overall, by the Washington Redskins.
On May 10, 2018, Guice signed a four-year, US$4.54 million contract with the team.
In the first preseason game of his rookie year, Guice sustained a torn ACL, which ended his season.

Guice made his regular season debut in the opening game of the 2019 season against the Philadelphia Eagles.
There, Guice rushed 10 times for 18 yards and caught 3 passes for 20 yards, but left the game with an injury to his right knee.
The Redskins would go on to lose the game 27-32.
It was later revealed that Guice had suffered a torn meniscus, requiring  surgery, with him being placed on injured reserve on September 13, 2019.
He was designated for return from injured reserve on October 28, 2019, and began practicing again with the team.
He was activated off injured reserve on November 7.

In Week 11 against the New York Jets, Guice rushed seven times for 24 yards and caught one pass for a 45-yard touchdown in the 34–17 loss.

In Week 13 against the Carolina Panthers, Guice rushed 10 times for 129 yards and two touchdowns in the 29–21 win.
The following week, he suffered an MCL sprain and was placed on injured reserve on December 10, 2019.
Guice was waived by the team on August 7, 2020, following charges of domestic violence.
In January 2018, Guice announced that he would forego his senior year at LSU in favor of the 2018 NFL Draft. Guice attended LSU's pro day in April 2018, but opted to stand on his combine numbers and only performed positional drills. At the conclusion of the pre-draft process, Guice was projected to be a first or second round pick by NFL draft experts and scouts. He was ranked among the best running backs of the 2018 class, 
Predicted as a first round pick before the draft, Guice reportedly had his draft stock fall due to questions about his character and other incidents during the drafting process, such as an alleged verbal altercation between himself and Howie Roseman, executive of the Philadelphia Eagles. Roseman and other Eagles personnel denied it took place, with Guice stating that the incident, as well as other rumors of him being lazy, immature, and dishonest, were not true. Another issue allegedly occurred at the NFL Combine, where Guice claimed that he was asked if he liked men during an interview with a team, as well as if his mother "sells herself". The NFL later investigated the claims, but found no proof it had happened. Guice was eventually drafted in the second round, 59th overall, by the Washington Redskins. On May 10, 2018, Guice signed a four-year, US$4.54 million contract with the team. In the first preseason game of his rookie year, Guice sustained a torn ACL, which ended his season.
Guice made his regular season debut in the opening game of the 2019 season against the Philadelphia Eagles. There, Guice rushed 10 times for 18 yards and caught 3 passes for 20 yards, but left the game with an injury to his right knee. The Redskins would go on to lose the game 27-32. It was later revealed that Guice had suffered a torn meniscus, requiring  surgery, with him being placed on injured reserve on September 13, 2019. He was designated for return from injured reserve on October 28, 2019, and began practicing again with the team. He was activated off injured reserve on November 7.
In Week 11 against the New York Jets, Guice rushed seven times for 24 yards and caught one pass for a 45-yard touchdown in the 34–17 loss.
In Week 13 against the Carolina Panthers, Guice rushed 10 times for 129 yards and two touchdowns in the 29–21 win. The following week, he suffered an MCL sprain and was placed on injured reserve on December 10, 2019. Guice was waived by the team on August 7, 2020, following charges of domestic violence.
Derrius Guice