Born on Aug. 9, 1977, in Queens, N.Y., Chamique Shaunta Holdsclaw lived with her protective grandmother, June Holdsclaw, from the age of 11. June served as Chamique's legal guardian, keeping her off the streets and occupied at Boys and Girls clubs or at church doing arts and crafts. While attending Christ the King High School, Chamique became the school's top scorer and rebounder while leading her team to four state championships and one national title. She wore the uniform number 23 not because it was Jordan's number, but for its religious significance: it represents the 23rd Psalm, which begins “The Lord is my shepherd, I shall not want.”

Holdsclaw chose to attend the University of Tennessee, where she majored in political science, because of the structure of coach Pat Summitt's program as well as the great fan support shown at the school for women's athletics. In her debut season of 1995–96, Holdsclaw led her team in both scoring (16.2 points per game) and rebounding (9.1 per game) en route to the NCAA championship game, in which she recorded 16 points and had 14 rebounds in a victory over Georgia. Named to the all–Final Four team, Holdsclaw also earned All American honors and recognition as the United States Basketball Writers Association's (USBWA's) rookie of the year.

In her sophomore year Holdsclaw again led the Lady Vols in scoring and rebounding, averaging 20.6 points and 9.4 rebounds per game, in addition to posting team highs in assists (114), steals (93), and blocked shots (35). Although the season was often a struggle as the team lost ten games, Tennessee played its best basketball of the season during the NCAA tournament. Holdsclaw led the way in the title game with 24 points and seven rebounds as the underdog Lady Vols defeated Old Dominion 68–59 to claim back-to-back championships. The most valuable player (MVP) of the Final Four and again a member of the all–Final Four team, Holdsclaw received first-team All American honors and was a finalist for the 1997 Naismith player of the year award.

Holdsclaw and the Lady Vols rose to new heights during the 1997–98 season. Widely hailed as the greatest women's basketball team ever, Tennessee routed Louisiana Tech by the score of 93–75 to record an unprecedented third consecutive NCAA championship and finish with a record of 39–0. Holdsclaw scored 25 points and grabbed 10 rebounds in the title game, an effort that earned her a second straight Final Four MVP award. Once again a first-team All American, Holdsclaw was recognized as the Naismith national player of the year in 1998, and her future plans became the subject of much speculation. Rather than challenge the rules that prohibited underclassmen from playing in the women's professional leagues, however, Holdsclaw insisted that she would return to Tennessee for her senior year.

During breaks from collegiate competition, Holdsclaw participated in national and international tournaments. At the 1995 United States Olympic Festival, she led the East Team to a gold medal and was named to the all-tournament team. In the summer of 1997 Holdsclaw played from South America to Europe as the only college player on the United States national team. With averages of 19.0 points and 6.2 rebounds per game, she finished as the squad's leading scorer and rebounder. In addition to winning the 1997 USA Basketball women's athlete of the year award, Holdsclaw earned one of six slots on the 1998 United States women's world championship team.