Reese attended Saint Frances Academy in Baltimore, Maryland, where she was awarded McDonald's All-American honors in 2020 and was ranked the number two player in her class by ESPN.

[7][8] She was coached by Ron James with Team Takeover, an Amateur Athletic Union (AAU) program based in Washington, D.C. that competes in the Nike Elite Youth Basketball League (EYBL), a national circuit.

[9] Her AAU teammates included Madison Scott, Mir McLean and Jakia Brown-Turner,[10][11] all of whom were given five-star ratings by ESPN at the end of their high school careers.

[12][13][14] Reese attended St. Frances Academy in Baltimore, Maryland, where she was a four-year varsity basketball player under head coach Jerome Shelton.

[20] Her team suffered its only loss to Hamilton Heights Christian Academy at the High School Nationals semifinals, where Reese recorded 20 points and 24 rebounds and made a putback shot to beat the buzzer and send the game to overtime.

[22] In her sophomore season, Reese repeated as an All-Metro first team selection, helping St. Frances win the IAAM A Conference championship and achieve a 24–4 record.

[17][26] Reese averaged 22.6 points and 19.3 rebounds per game as a junior and was named All-Metro Player of the Year by The Baltimore Sun after leading St. Frances to the IAAM A Conference title.

[27] That year, she led Team Takeover to the Nike EYBL championship, posting 18 points and 11 rebounds in a 57–47 win over All Iowa Attack in the final.

[28] In January 2020, Archbishop Spalding High School head coach Lisa Smith was fired from her position after her private messages on Instagram criticizing Reese's behavior were made public.

[16] As a senior, she averaged 18.6 points, 10.2 rebounds, 3.4 assists and 2.5 blocks per game, winning her fourth straight IAAM A Conference championship and helping her team finish with a 25–3 record.

[6][32] By her junior season of high school, she held scholarship offers from over 24 NCAA Division I basketball programs, including Maryland, South Carolina and Louisville.

[54] She led fourth-seeded Maryland to the Sweet 16 of the 2022 NCAA tournament, where she recorded 25 points, 9 rebounds, 3 steals and 3 blocks in a 72–66 loss to first-seeded Stanford on March 25.

[75] Reese helped LSU win its first national championship, posting 15 points, 10 rebounds and five assists in a 102–85 victory over Iowa in the title game.

Her actions came under scrutiny, with some journalists and analysts criticizing her for poor sportsmanship and others, including Reese herself, pointing to a double standard, because Clark had not received similar backlash for making the "you can't see me" gesture two games earlier.

[78] The incident drew attention to the roles of race and gender in the perception of trash talk in sports since Reese is Black and Clark is white.

[93][94] LSU was ranked number one by the AP in its preseason poll, with incoming transfers Hailey Van Lith and Aneesah Morrow.

[101] At the end of the regular season, Reese was named SEC Player of the Year while earning first-team All-SEC and All-Defensive Team recognition from the league's coaches.

[102] She led LSU to the Elite Eight of the 2024 NCAA tournament, where she had 17 points and 20 rebounds in a 94–87 loss to one-seed Iowa in a rematch of the 2023 national championship game.

[108] On June 20, she had her seventh consecutive double-double, the longest such streak by a WNBA rookie, after posting 16 points and 18 rebounds in an 83–72 win over the Dallas Wings.

[110] On June 30, she registered her 10th straight double-double, with 10 points and 16 rebounds in a 70–62 loss to the Minnesota Lynx, surpassing Candace Parker of the Los Angeles Sparks for the longest single-season streak in WNBA history.

[113] On July 7, Reese had her 13th consecutive double-double, with 17 points and 14 rebounds in an 84–71 loss to the Seattle Storm, and passed Parker for the longest streak across multiple seasons.

[115] Reese became the first rookie to have a double-double in WNBA All-Star Game, finishing with 12 points and 11 rebounds in a 117–109 win over the United States national team.

[117] On September 1, Reese broke the WNBA single-season rebounding record held by Sylvia Fowles as part of a 17-point, 19-rebound effort in a 79–74 loss to the Minnesota Lynx.

[118] Reese's rookie season ended on September 6, when she sustained a hairline fracture in her wrist during the Sky's game against the Los Angeles Sparks.

[120] On July 24, 2024, it was announced that Reese would appear and play in the inaugural season of Unrivaled, a new women's 3x3 basketball league founded by Napheesa Collier and Breanna Stewart.

[159] Reese has also signed deals with Amazon, Bose, Coach, Discord, Outback Steakhouse, Sonic, TurboTax, Wingstop and Xfinity, among other companies.

The nickname refers to the location of the school, in Baton Rouge, Louisiana, and her appearance on the court, with eyelash extensions and long pink nails.

[167] She credits a fan in Baton Rouge with creating the nickname, and she filed for a trademark on the "Bayou Barbie" in her first season at LSU but was denied.

Johnson's skit parodied Reese's gesture at the end of the 2023 NCAA Division I championship game and her dispute over Jill Biden's comments about inviting Iowa to the White House.

[185][186] In January 2025, Vogue magazine announced that Reese is the cover star of their winter issue, profiling the convergence of sports and fashion in her career.