During his time as an assistant coach at the Academy, Popovich earned a master's degree in physical education and sports sciences from the University of Denver.

From 1988 to 1992, Popovich was Brown's top assistant, until the entire staff, including R. C. Buford, Alvin Gentry and Ed Manning, were fired by owner Red McCombs.

Popovich moved to the Golden State Warriors for a brief stint in 1992, serving as an assistant under future Hall of Famer Don Nelson and bringing with him Avery Johnson, who had been cut by the Spurs.

In 1994, Popovich returned to San Antonio as the general manager and vice president of basketball operations after Peter Holt purchased the team.

With a reduced roster that included an aging Dominique Wilkins, the Spurs struggled and won only 17 games for the remainder of the season for an overall record of 20–62.

[27] On November 29, 2012, Popovich sat out starters Tim Duncan, Tony Parker, Manu Ginóbili, and Danny Green for a nationally televised game against the Miami Heat.

Popovich frequently sat out his starters on road trips over the years to ensure they have enough rest for the playoffs; the Spurs' roster was among the oldest in the league.

According to Stern, Popovich had not informed the Heat, the league or the media in a suitable time frame that the four players were not making the trip to Miami.

On February 9, 2015, Popovich became the ninth coach in NBA history to win 1,000 games when the Spurs defeated the Indiana Pacers 95–93.

[32] In the 2015–16 season, Popovich led the Spurs to a franchise-high 67 wins, but he and the team lost in the conference semifinals against the Oklahoma City Thunder in six games.

[33] On April 13, 2019, Popovich surpassed Lenny Wilkens and became the all-time winningest coach in NBA history with his 1,413th win (regular season and playoffs combined).

[35][36] On January 26, 2020, the Spurs hosted the Toronto Raptors just hours after a California helicopter crash claimed the lives of nine people, including NBA legend Kobe Bryant and his 13–year-old daughter Gianna, and Popovich proposed that both teams take an intentional 24-second shot clock violation on each of their first possessions to pay homage to Bryant's jersey number 24, which he donned from 2006 to 2016.

[37] On March 27, 2021, after leading his team to a 120–104 victory against the Chicago Bulls, Popovich won his 1,300th regular season game and became the third NBA coach to reach the milestone.

Two days later, it was announced that he would need to take an indefinite break from work, with assistant Mitch Johnson stepping in as interim head coach.

[44][45] Popovich served on the coaching staff for the U.S. men's national team during the 2002 FIBA World Championship (assisting George Karl),[46] during the 2003 FIBA America Men's Olympic Qualifying Tournament, and during the Athens 2004 Olympic Games (assisting Larry Brown), where the U.S. team won the bronze medal.

On October 23, 2015, Popovich was named the head coach of the U.S. men's national team, taking over from Mike Krzyzewski after the Rio 2016 Olympic Games.

[52] On multiple occasions, Popovich has spoken out on behalf of social justice issues, including in support of the 2017 Women's March.

[57] Popovich has spent considerable time and money working with several charities and nonprofits such as the San Antonio Food Bank and the Innocence Project.