Johnson attended Miami Norland Senior High School in Miami Gardens, Florida, where he played football and ran track. He was coached by Daryle Heidelberg. As a sophomore, Johnson ran for 1,540 yards and 25 touchdowns. In his junior year, he led Norland to a 13–2 record and state runner-up. After beating the Sammy Watkins-led South Fort Myers 44–28 in the semifinals, Norland lost 44–34 to the unbeaten Tampa Jefferson in the class 3A final. During his senior year, Johnson compiled 1,957 rushing yards and 29 touchdowns, 14 receptions for 232 receiving yards and three touchdowns, three kickoff returns and one punt return for scores, as he led Miami Norland to 14–0 finish and state Class 5A championship. In the championship game against Wakulla, he scored five touchdowns.
He was also on the school's track & field team, where he was an standout sprinter and long jumper. He placed 5th in the long jump event at the 2010 GMAC Qualifiers, with a jump of 6.60 meters. In 2011, he placed 4th in the 100 meters at the 3rd Annual Miramar Invitational, recording a career-best time of 10.62 seconds. He finished 3rd in the 200 meters at the FHSAA 3A District 16, with a time of 22.31 seconds.
He was considered the best all-purpose running back recruit by Rivals.com.
In his freshman season, Johnson rushed for 947 yards on 139 carries with ten touchdowns, and caught 27 passes for 221 yards and one touchdown. He also threw an additional touchdown during a game vs. Virginia. He also played a major role on special teams, where he returned 28 kicks for two scores. In 2012, Duke Johnson won both the ACC Rookie of the Year and Offensive Rookie of the Year awards. He is the first Miami Hurricane to win both awards. In 2013, Duke Johnson joined the Miami indoor track team, posting a personal-best time of 6.92 seconds in the 60 meters at New Mexico Classic. Johnson's sophomore campaign with the Hurricane's football team came to an abrupt end November 2, 2013, when he broke his ankle against arch-rival Florida State. UM went on to lose that game 41-14. Through eight games, Johnson rushed for 920 yards on 145 carries, with six touchdowns. He also had four catches for 77 yards. Johnson returned from the injury his junior season in 2014 to play in all 13 games. During the season, he passed Ottis Anderson to become the Hurricane's all team rushing yards leader. He ended the year with 1,652 yards and 10 touchdowns.
After his junior season, Johnson entered the 2015 NFL Draft. He finished his college career with 3,519 rushing yards on 526 carries with 26 touchdowns.