As a player, Scheyer led his high school team to an Illinois state basketball championship as a high school All-American, and was the captain of the 2009–10 Duke Blue Devils that won the 2010 NCAA Basketball Championship, as a college All-American.

He was a prolific high school scorer, and later an Atlantic Coast Conference (ACC) leader in numerous statistical categories, including free-throw percentage, three-point shots/game, and assists/turnover ratio.

"[8] Scheyer attended Glenbrook North High School and led the Spartans to an Illinois High School Association Class AA state basketball championship as a junior, a 3rd-place finish in 2003 as a freshman, and an Elite Eight appearance in the state playoffs three out of four years from 2003 to 2006.

"[24] Scheyer rose to national fame in his senior year by scoring 21 points in 75 seconds of play during a one-man comeback effort in the last minute and a half of a high school game against Proviso West High School, in an effort to keep alive his team's 35-game winning streak.

[23] One example of his dogged pursuit of excellence is that while in high school, Scheyer refused to leave the gym one night until he made 50 consecutive free throws.

[17][21] He was named Illinois Mr. Basketball in 2006 by an overwhelming margin (receiving 217 votes, to 17 for the second-place finisher), a high school All-American, a two-time Gatorade state Player of the Year, and a three-time All-State selection.

[33] Working in favor of Duke, however, was the fact that its assistant coach Chris Collins had also attended Glenbrook North.

[23] In the 2006–07 season he started all 33 Blue Devils games as a freshman,[35] and scored a season-high 26 points in a loss to North Carolina on February 7, 2007.

[23] He had a team-best 2.24:1 assist-to-turnover ratio, averaged the third-most minutes-per-game on the team (28.3), was fourth in scoring (11.7), and was widely hailed as one of the country's top sixth men.

Florida State Seminoles men's basketball coach Leonard Hamilton said he thought Scheyer had a "calming" influence on the team's offense.

"[52] On December 2, 2009, he became the first Duke player to record 1,400 points, 400 rebounds, 250 assists, 200 3-point field goals, and 150 steals for a career.

[54] Scheyer made a 3-pointer with 18 seconds left to seal a win for Duke over Georgia Tech for the ACC championship on March 14, 2010.

[56] In Duke's Final Four win over West Virginia, he led the team with 23 points while shooting 5 for 9 from 3-point range, with 6 assists, no turnovers, and 2 steals.

[57] Duke won the national championship with a 61–59 victory over Butler, as Scheyer scored 5 of the team's last 10 points.

[71] Scheyer set the ACC all-time single-season record for minutes played in 2009–10 (with 1,470, passing Dennis Scott).

[37][72][76] In addition, he had 208 steals (8th in school history, behind Grant Hill), and had scored 2,077 points (9th on Duke's all-time list, behind Jason Williams and Gene Banks).

[85][86] Scheyer played on the Miami Heat's 19-man 2010 NBA Las Vegas Summer League team.

[16] In the team's second game, however, in mid-July, he was poked in the eye by Golden State's Joe Ingles.

[16][88][89] He needed five stitches to close a cut to his right eyelid, his eye's optic nerve was injured, and he suffered a tear in its retina, which was surgically reattached.

[16][91][93] Maccabi Tel Aviv coach David Blatt also approached Scheyer about playing in Europe.

[94] On September 22, 2010, Scheyer accepted a training camp invitation with the NBA's Los Angeles Clippers.

[96][97] After some additional time off to recover from his injury, on February 17, 2011, Scheyer signed a contract with the Rio Grande Valley Vipers, the Houston Rockets D-League team, which had 16 games left in their season.

[92][101][102] In 24 regular and post-season games, he averaged 13.1 points, 4.0 assists, and 4.0 rebounds as the team finished the season as runner-up in the championship.

[92][93] In June 2011, Scheyer signed a two-year contract worth a reported $450,000 with Euroleague contender Maccabi Tel Aviv, the European league's 2011 runner-up and five-time champion.

[103][104][105][106] Maccabi Tel Aviv was 26–1 in 2010–11, and included NBA guard Jordan Farmar and former American college players Richard Hendrix (Alabama), Shawn James (Duquesne), and David Blu (University of Southern California).

[109] The team was limited to no more than four players who are non-Israeli, but because Scheyer has a Jewish father he had the ability to obtain Israeli citizenship relatively quickly, and did so in September 2011.

[105] "I am really excited to take the next step in my basketball career and go play for Maccabi Tel Aviv," said Scheyer.

[125] With the departure of Steve Wojciechowski from the Blue Devils staff, Scheyer was promoted to a full assistant coach on April 18, 2014.

[127] Scheyer served as acting head coach for Duke's 83–82 win over Boston College on January 6, 2021, filling in for Krzyzewski who had to miss the game because he was quarantined after being exposed to COVID-19.

[128] On June 2, 2021, it was announced that Scheyer would become Duke's next head basketball coach after Mike Krzyzewski's retirement following the end of the 2021–22 season.