Little attended Hillside High School in Durham, North Carolina, graduating in the spring of 2007.
Little mostly played tail back for his junior year and some wide receiver. His vertical jump was 40.0" and his broad jump was 10-1. North Carolina, Florida, Michigan, Notre Dame, Ohio State, and USC all offered him to go to their college. He visited North Carolina 10/13/2006, Notre Dame 9/16/2006, and Ohio State 9/23/2006. He later on verbally committed to The Universality of North Carolina. During School his GPA was a 2.7 and had a 930 SAT.
As a senior in 2010 Little didn't play any games after he was ruled ineligible by the NCAA for lying to investigators about receiving travel accommodations and jewelry.
As a freshman in college, 2007, he had a total of 300 rushing yards and 99 receiving yards. Little also returned kick-offs and had a total of 145 yards. As a Sophomore, he had a total of 339 rushing yards and 146 yards receiving. For kick-offs he had a total of 141 yards. Lastly, as a Junior, Little had 166 rushing yards and 724 receiving yards. Also, kick-offs he had 222 returning yards. 
Greg Little finished the 2011 season leading the Cleveland Browns in catches and receiving yards. Little was second amongst rookies in catches, behind first round pick A. J. Green and fifth in yards behind Green, Torrey Smith, Julio Jones, and Doug Baldwin. He also finished with two touchdowns.
He has struggled with drops in 2012.