As with each All-Star Game since 1970, the 8 starting position players of each league were elected by fan balloting. The remaining players were selected by a players' vote, each league's team manager, and the All-Star Final Vote to add one more player to each roster. In all, 32 players were selected to each league's team, not including players who decline to play due to injuries or personal reasons. The game was the fourth straight All-Star Game to decide home-field advantage in the World Series. The AL entered the game on a nine-game unbeaten streak. Many analysts saw the disparity between the leagues as more pronounced than ever this season, particularly due to the AL's dominance during interleague play, compiling a 154–98 record, the best record for either league in the ten-year history of interleague play.
National League starting pitcher Brad Pennyset the tone for the evening, striking out Ichiro Suzuki, Derek Jeter, and David Ortiz to start the game. His fastball had uncharacteristic speed, never going below 96 miles per hour, and – aside from a lone curveball – was the only pitch he threw in the first inning. American League pitcher Kenny Rogers wasn't as overpowering as Penny, but still escaped the first relatively unscathed. The AL would get to Penny in the second as Vladimir Guerrero hit an opposite-field home run that just cleared the right field fence, giving the AL a 1–0 lead. The NL would respond in the bottom of the inning with David Wright hitting his own home run to left field, tying the game at 1–1. Roy Halladay relieved Rogers in the bottom of the third. It was in this inning when the National League exemplified what it does best: playing small. Alfonso Soriano hit a single with one out and stole second base on Gold Glove catcher Iván Rodríguez. He tried to score on a single by Carlos Beltrán, but was thrown out at home plate by Vernon Wells. Beltran would advance to second on the throw, then steal third and score on a wild pitch by Halladay, giving the NL a 2–1 lead. That lead would seem like enough for the NL for most of the evening. After Roy Oswalt relieved Penny in the third, Brandon Webb, Bronson Arroyo, Brian Fuentes, Derrick Turnbow, and Tom Gordon would each throw an inning of scoreless relief, limiting the AL to just three hits in that span. After Halladay pitched the fourth, Barry Zito, Scott Kazmir, Johan Santana, and B.J. Ryan would also each pitch an inning without giving up a run, with the only baserunner allowed on a walk by Santana, the only walk of the game. Trevor Hoffman came on to try to earn the save in the ninth. After inducing two groundouts back to himself, it seemed like Hoffman, who, at the time, was second all-time in career saves, would finally send the American League to a loss in an All-Star Game for the first time in a decade. However, Paul Konerko hit a single to left past third basemanMiguel Cabrera, and was pinch-run for by José Lopez. Troy Glaus hit a ground rule double down the left field line, forcing Lopez to hold at third. While it looked like the National League received a break, Hoffman allowed a two-strike triple to Michael Young, who went on to win the MVP, scoring Lopez and Glaus and putting the AL up 3–2. Mariano Rivera would now try to save the game for the American League. Because Lopez pinch-ran for Konerko in the top of the ninth, the American League was left without any first basemen on the roster. Glaus, in the game as a third baseman, moved to first for the bottom of the inning, a position he never played before in his career, while Lopez played third. Despite an error made by Lopez, Rivera pitched a quiet ninth to earn the save and extend the American League's unbeaten streak to ten games.
The Century 21 Real Estate Home Run Derby was held on the Monday before the game, July 10. Four players from each league competed to hit as many home runs in each round to advance and eventually win the contest. This year's Derby featured an important rule change: home runs in the first round would carry over into the second round. In previous years, some players would hit a tremendous amount of home runs in the first round, but become tired by the second round and hit relatively fewer home runs for that round, often not enough to qualify for the finals. By allowing the home runs to carry over, a player can't necessarily be "punished" for hitting an impressive total in the first round. However, like in previous Derbies, the two finalists start over at zero for the finals. In the finals, Ryan Howard of the Philadelphia Phillies defeated David Wright of the New York Mets 5–4, and hit a total of 23 home runs on the night, leading all competitors. Howard memorably hit his winning home run into a sign guaranteeing one person in the crowd 500 free round-trip flights from Southwest Airlines. PNC Park is distinct for having the Allegheny River running behind the right field bleachers. As a result, several balls were hit into the riveron the fly, as well as many more bouncing off the walkway alongside the river. Many fans waited in the river in canoes hoping to retrieve a ball, a sight more reminiscent of the following year's All-Star Game and Home Run Derby site, AT&T Park. For the second straight year, gold balls were utilized whenever a player had one out remaining in the round. Any home runs hit with the gold ball meant Major League Baseball and Century 21 would pledge to donate $21,000 to the Boys & Girls Clubs of America and Easter Seals, respectively. In all, 14 gold-ball home runs were hit, constituting $294,000 raised for both charities.
Commissioner Bud Selig presented the Commissioner's Historic Achievement Award to deceased Pittsburgh Pirates legend Roberto Clemente between the fourth and fifth innings of the All-Star Game. Clemente's widow, Vera, accepted the award. FOXplay-by-play announcerJoe Buck emceed the ceremony. As a result, he called the bottom of the fourth inning from the entrance behind home plate. Buck created a little controversy when after Vera Clemente spoke what many said was a beautiful, moving speech Buck asked the fans "You guys having fun out here?!"
