He played college football for the LSU Tigers, where he was the first player in Southeastern Conference (SEC) history with three career games of 250 or more rushing yards before being selected by the Washington Redskins in the second round of the 2018 NFL draft.

Guice appeared in just five games in two years in the NFL due to multiple knee injuries and was released in 2020 after being charged for crimes related to domestic violence.

LSU disassociated itself from Guice and removed all of his statistics from their record books in 2021 amid claims that the school had mishandled accusations of multiple rapes committed by him during his time there.

[1] Over the course of his junior year, Guice began spending more time at the de la Houssaye household, eating dinner with her and her husband and children and going on vacations with them, eventually moving in with them.

Catholic went 9–2 on the season and lost 25–23 to New Orleans Brother Martin in the LHSAA Division I quarterfinals at BREC Memorial Stadium, after Guice was stopped on a two-point conversion that would have tied the game.

[8] He committed to Louisiana State University (LSU) to play college football, fulfilling a promise he made to his father before his death.

[14] He became only the fourth running back in Southeastern Conference history to record multiple 250-yard rushing performances in a career, following Bo Jackson, Herschel Walker, and Moe Williams.

Guice attended LSU's pro day in April 2018, but opted to stand on his combine numbers and only performed positional drills.

[22][23] 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.

[22][23][24][25] 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".

[45] Guice was the first athlete to sign with Top Dawg Entertainment's sports division agency, a record label better known for representing musical artists such as Kendrick Lamar and Schoolboy Q.

[50][51] In November 2016, Guice's brother Derrick was arrested and charged with attempted second-degree murder following an incident where he was the driver of two gunmen who shot at a man on his porch in Baton Rouge.

[52] On August 7, 2020, Guice was arrested and charged with counts of strangulation, assault, battery, and destruction of property that stemmed from three separate domestic violence incidents that had taken place at his home in Loudoun County, Virginia earlier that year.

[53] Soon after the rape accusations were made public, another former LSU student announced that she had filed a police report against Guice in 2016 for taking a partially nude photograph of her without her knowledge and sharing it with some of his football teammates, a felony under Louisiana law.