By the time Rose enrolled at Simeon Career Academy in 2003, he was a hot commodity for collegiate coaches. Despite his reputation, he played freshmen and JV basketball for the Wolverines. He wore No. 25 in honor of Ben "Benji" Wilson, a promising player who was murdered by a gang member during his senior year in 1984.Rose was not allowed on varsity due to a long-standing tradition that head coach Bob Hambric, who had been with the school since 1980 had no freshmen on the varsity team. That rule did not lessen Rose's play, and he went on to put up 18.5 points, 6.6 assists, 4.7 rebounds and 2.1 steals per game and led both the freshmen and sophomores to city championships with a 24–1 record.Ham bric softened his stance and allowed the freshman a chance to play on varsity in the state tournament, but Rose declined, wanting the players to get due credit.The next year Hambric retired and Robert Smith was hired, opening the path to varsity. In Rose's debut, he had 22 points, 7 rebounds and 5 steals over Thornwood High School in a sold-out game filled with college scouts and coaches.He led the Wolverines to a 30–5 mark while averaging 19.8 points, 5.1 rebounds, 8.3 assists and 2.4 steals but the season ended after a loss in state regionals. Rose's play garnered him his first national award: a Parade All-American third team spot.
During Rose's junior year in 2006, the Simeon Wolverines broke through and won the Chicago Public League championship held at the United Center, where Rose starred with 25 points and crowd pleasing dunks. The team advanced through the playoffs and earned a berth in the Class AA state championship against Richwoods High School, where a fourth quarter buzzer beater by Richwood forced overtime. The score was knotted at 29 late in the extra period when Rose stole the ball and buried the game winning jumper as time expired, giving Simeon its first state title since the Wilson-led Wolverines won in 1984. The team finished 33–4 and ranked nationally,and Rose was awarded with an All-State Illinois mention, EA Sports All-American Second Team pick and another Parade All-American selection.
Entering his senior year, Rose was ranked the fifth best prospect in the nation by Sports Illustrated. In January 2007, Simeon traveled to Madison Square Garden to play Rice High School and star guard Kemba Walker.The Wolverines lost 53–51.The season's highlight was a nationally televised contest on ESPN against Virginia perennial power Oak Hill Academy two weeks later. Matched up with hyped junior guard Brandon Jennings, Rose had 28 points, 9 assists, and 8 rebounds and in a 78–75 win.For his performance, USA Today named him their high school player of the week. Simeon went on to repeat as Public League champions and defended their state championship, defeating O'Fallon High School 77–54.In doing so, Simeon became the first Chicago Public League school to win two straight state championships. In his final high school game, Rose scored 2 points, but pulled down 7 rebounds and totaled 8 assists, while Simeon big man Tim Flowers scored 35 points.The Wolverines ended the season 33–2 and ranked first in the nation by Sports Illustrated and 6th on USA Today's Super 25.Rose averaged 25.2 points, 9.1 assists, 8.8 rebounds and 3.4 steals.
Overall, Simeon's record while Rose played was 120–12.After his senior year, Rose was again All-State after being named Illinois Mr. Basketball and was named to the McDonald's All-American team.He was also awarded with First Team honors by Parade selection and USA Today and USA Today First Team All-American.
Rose was selected to play in the Jordan Brand All-Star Game and Nike Hoop Summit. In 2009, Rose was named the decade's third greatest high school point guard by ESPN RISE magazine behind Chris Paul and T.J. Ford,and had his jersey number #25 retired along with Ben Wilson.
