In 2008, his freshman year at Hillcrest High School, Green-Beckham caught 37 passes for 801 yards and 13 touchdowns. As a sophomore, he posted 66 catches for 1,616 yards and 23 touchdowns. As a junior in 2010, Green-Beckham was the Rivals High School Football Junior of the Year after he had 78 receptions for 1,706 yards with 15 touchdowns. As a senior, Green-Beckham had 119 receptions for 2,233 yards with 24 touchdowns. In October, he became the nation's all time leading high school receiving yards leader, a record broken on November 16, 2013, by Trey Quinn, a Lake Charles, Louisiana, receiver from Barbe High School.  For his play he was named the Sporting News High School Athlete of the Year. He played in the 2012 U.S. Army All-American Bowl.
One of the most highly regarded football recruits of the class of 2012, Green-Beckham was listed as the number one overall prospect in the nation by Rivals.com. He is considered the third best by Scout.com, ESPN and Sporting News. In January 2012 he narrowed his college decision to Alabama, Arkansas, Missouri, Oklahoma and Texas, and he stated that he would make his decision on National Signing Day (February 1, 2012). In a nationally-televised ceremony, Green-Beckham announced he would sign a national letter of intent to attend the University of Missouri. Said Green-Beckham of his decision, "just to stay home and have all those guys [family, friends] come out and see me [was big]." He picked Missouri over SEC-rival Arkansas, also because offensive coordinator Garrick McGee, who had formed a strong relationship with Green-Beckham and his family, left the school in December 2011.
Green-Beckham is also a standout track star. In the state Class 4 track and field finals in 2011, he claimed titles in the 100 meters, with a time of 10.92 seconds  and in triple jump, with a leap of 14.39 meters, and was also second in the long jump, with a leap of 7.14 meters.
Looking to receive playing time as a true freshman, Green-Beckham was likely play the "X" receiver position in Missouri's offense, the same one prolific pass-catchers like Michael Egnew and Danario Alexander have thrived in, of late. He appeared in the first five games of the season, registering five catches for 125 yards, including an 80-yard touchdown reception against Central Florida. Then came an arrest and suspension due to drug possession, causing Green-Beckham to miss the Vanderbilt and Alabama game on October 6 and 13, respectively.
Green-Beckham returned for the second half of the season on October 27 against Kentucky, catching a season-high seven throws for 25 yards. In a 7–14 loss at Florida, he totalled six catches for 75 yards. Then, in a four-overtime 51–48 win over Tennessee, Green-Beckham had two catches, both for touchdowns, and for 35 yards. In the final minute of regulation, he caught a game-tying touchdown in the left corner of the end zone. Against Syracuse and Texas A&M, he added two and four catches, for 79 and 55 yards, respectively. For his freshman season, he had 28 receptions for 395 yards and a team-best 5 receiving touchdowns, which earned him honorable mention freshman all-American honors by College Football News.
Green-Beckham was born Dorial Green as the third of six children born to Charmelle Green, a single mother, in St. Louis, Missouri. He never knew his biological father. He lived in several foster homes before John Beckham, his high school coach, and his wife Tracy officially adopted him on December 30, 2009. The Beckhams had brought Green and his younger brother Darnell into their home in 2006. The couple has one other child, a young daughter, who Dorial is very close to. Darnell Green-Beckham is currently receiving treatment for acute lymphoblastic leukemia but is in remission.
Late on the night of October 3, 2012 Green-Beckham and two other freshman teammates, linebacker Torey Boozer and receiver Levi Copelin, were arrested on drug charges by the University of Missouri police department after the three were found in possession of 35 grams (1.2 oz) or less of marijuana. Green-Beckham and the others were parked in a vehicle south of Memorial Stadium in Columbia at the time of their arrest. Two other unnamed individuals—also Mizzou players—were in the vehicle as well, but were released after police determined they were not involved in the drug possession. After being processed at the campus police station Green-Beckham, Boozer, and Copelin were released on signature summons. In response to the arrest a spokesperson for the MU athletic department said that all five players would be suspended from the next game, October 6 against Vanderbilt. Other disciplinary action may also be taken by the team and handled internally with no additional public comment on the issue. The case was resolved on October 16, 2012 when Green-Beckham entered a guilty plea to a reduced charge of tresspassing in Columbia, Missouri Municipal Court. He was fined $200 plus court costs.