In attendance at the announcement was NBA Commissioner Adam Silver, Pacers owner Herb Simon, Governor Eric Holcomb, and Mayor Joe Hogsett.

[6] The two teams played in support of the Thurgood Marshall College Fund and United Negro College Fund respectively, recorded performances of bands from Florida A&M University and Grambling State University were used for player introductions, and the court was decorated with artwork from students of HBCUs.

[9] The NBA faced criticism for going on with the All-Star Game, raising the possibility of a superspreading event due to participation by players from multiple teams.

[12] Multiple players expressed resentment to the decision, including Carmelo Anthony, LeBron James (who described it as a "slap in the face"), and Kawhi Leonard among others.

[11][13][10] Critics acknowledged that the All-Star Game has been a major source of revenue for the NBA and its media partners which likely factored into the decision to still go on with the event.

[15] Spectators were limited to 1,200–1,500 invited guests and were expected to include vaccinated health care workers and the students and faculty of HBCUs.

[12][11] This request was enforced by the NBA which sent cease-and-desist notices to various local businesses for using its trademarks to promote events tied to the All-Star Game.

[17] Artificial crowd noise and virtual fans on screens along the court, similarly to the NBA Bubble, were also utilized.

Bradley Beal of the Washington Wizards and Kyrie Irving of the Brooklyn Nets were named the backcourt starters in the East, earning their third and seventh all-star appearances, respectively.

Kevin Durant of the Brooklyn Nets and Giannis Antetokounmpo of the Milwaukee Bucks were named the frontcourt starters in the East, earning their 11th and fifth all-star appearances, respectively.

[23] Luka Dončić of the Dallas Mavericks and Stephen Curry of the Golden State Warriors were named to the starting backcourt in the West, earning their second and seventh all-star appearances, respectively.

[27] ^ST2 Zion Williamson started in place of Joel Embiid on Team Durant, who was out for the game due to contact tracing in addition to his teammate Ben Simmons.

Hours before the opening tip, the 76ers' Embiid and Simmons were scratched from the game due to NBA COVID-19 protocols as they had visited a local barber in Philadelphia who later tested positive before they traveled to Atlanta.

[31] Giannis Antetokounmpo scored 35 points on a perfect 16-of-16 shooting from the field to lead Team LeBron to a 170–150 win and capture All-Star MVP honors.

[31][7] Damian Lillard and Stephen Curry added 32 and 28 points, respectively, and both made eight three-point field goals for Team LeBron, including several from more than 30 feet from the basket.

[32] The game used the same format as the 2020 edition: the team that scored the most points during each of the first three 12-minute quarters would receive a cash prize to be donated to a designated charity.

A Rising Stars roster was named to honor the league's top first- and second-year players, but the game was not played.

[31][36] Curry won his second Three-Point Contest after making his last shot in the final round to edge Mike Conley Jr.

[41][42] Additionally, this was the final NBA All-Star Game to ever be called by Marv Albert, as he announced his retirement from broadcasting following the 2021 Playoffs.