The 2010 Major League Baseball All-Star Game was the 81st midseason exhibition between the All-Stars of the American League (AL) and the National League (NL), the two leagues comprising Major League Baseball. The game was held on July 13, 2010, at Angel Stadium of Anaheim, the home of the American League Los Angeles Angels of Anaheim, and was telecast by Fox Sports in the US, with Joe Buck and Tim McCarver in the broadcast booth. Fox also teamed with DirecTV to produce a separate 3D broadcast, the first ever for a network Major League Baseball game. Kenny Albert and Mark Grace called the 3D telecast. ESPN Radio also broadcast the game, with Jon Sciambi and Dave Campbell announcing. The National League won the game 3–1, ending a 13-game winless streak.

This was the third All-Star Game hosted by the city of Anaheim, California, which previously hosted the game in 1967 and 1989. From 2003 to 2016, the winning team earned home field advantage for the World Series. This was the first All-Star Game the National League won since 1996, giving the NL said advantage in the World Series for the first time since 2001 – ironically, the winning pitcher, Washington Nationals closer Matt Capps, would go on to participate in the American League playoffs after his trade to the Minnesota Twins just a couple of weeks following the Midsummer Classic.

A short memorial honoring George Steinbrenner, the owner of the New York Yankees who died early that morning, was held prior to the game.

The 2010 All-Star Game marked the first time major changes took place since the 2003 decision to begin handing home field in the World Series to the winning league. The designated hitter became a permanent fixture of the game regardless of site (a change which became more noticeable when the game was next played in a National League park – in 2011 at Chase Field in Phoenix). But, continuing with past precedent, whereas fans voted the American League starter in, as they did in previous years when an A.L. city hosted the game, the National League's manager continued to name his team's DH before the game from the list of reserves (player-elected and manager-chosen).

Other changes included having the rosters of each league team increased to 34 players. Pitchers who started the regular-season game on the Sunday immediately before the game became ineligible to pitch in the game, and were replaced on the roster (this rule would be invoked for three players selected for the American League squad – Trevor Cahill, CC Sabathia and Jered Weaver). As with any player ineligible or unable to play, each was still recognized as an All-Star.

Finally, a modified re-entry rule also made its debut (though saw no usage in this contest). In addition to the existing injured catcher rule, the manager was now allowed to select one position player to re-enter a game in the event that the last available position player at any position is injured.

After the rosters were revealed, a second ballot of five players per league was created for the All-Star Final Vote to determine the 34th and final player of each roster, with online balloting conducted from Sunday afternoon, July 4, through Thursday afternoon, July 8. The winners of the final vote were Nick Swisher of the New York Yankees and Joey Votto of the Cincinnati Reds.

§ – When Bell replaced Yovani Gallardo due to injury on Wednesday, July 7, his name was withdrawn from the Final Vote ballot.