By the time he was a high school freshman, he shared the backfield duties for the IHSA state Class 5A runner up.

[4][5] During his junior season, he rushed for 2,629 yards and 51 touchdowns, including a 515-yard, 6-touchdown effort in the 2011 IHSA Class 5A championship game against Montini Catholic High School.

[6] However, Isaac also lost two fumbles and threw an interception in what turned out to be a 70–45 championship game loss.

[8] At the end of the season, he earned the 2011 Chicago Sun-Times Football Player of the Year award.

[5] He endured a shoulder sprain and a groin injury that year but still managed to compile nearly 1,500 yards and 20 touchdowns.

[13][14] His 44-yard, 8-carry 2013 Las Vegas Bowl performance against Fresno State, which included a 35-yard reception, was also considered a sign of his potential.

[16] He decided to transfer following his freshman season, and cited geographic distance from his ailing mother as his reason for wanting to return to the midwest.

[19] His request to play immediately for the 2014 Wolverines was denied by the National Collegiate Athletic Association.

[20] Isaac debuted for Michigan on September 5, 2015, gaining 12 yards on four carries as a backup player in the season opener against Utah.

[24][25] After the Maryland game, Isaac's playing time dropped sharply, carrying the ball only twice against Northwestern and twice against Minnesota.