Zack Greinke, the starter for the National League, allowed a home run to the first batter he faced -- Mike Trout of the Angels.
Clayton Kershaw struggled even more, and ended up taking the loss for the NL after the American League won, 6-3, before a sold-out crowd at Great American Ball Park.
"It was fun until I started giving up runs," Kershaw, the reigning NL MVP, said. "I felt fine. I wasn't really worried about throwing the ball where I wanted to. I was just trying to get people out."
After nearly not even making it to Cincinnati, added to the roster on Sunday as a replacement for Max Scherzer of the Nationals, Kershaw entered the game in the fifth inning with the score tied at 1.
Like Greinke, he looked anything but invincible.
Kershaw allowed a single to Alcides Escobar of the Royals, though Escobar was erased on a fielder's choice. Later in the inning, Manny Machado just missed what would have been a two-run homer when he flied out to the wall in left field.
Kershaw's outing then took a turn for the worse. After Albert Pujols of the Angels walked, Prince Fielder of the Rangers lined an RBI single to left field, and the AL took a one-run lead. Lorenzo Cain of the Royals then added an RBI double down the left-field line to make it 3-1.
Kershaw got out of the inning when he struck out pinch-hitter Brett Gardner of the Yankees for the third out.
"Obviously. Kershaw is awesome, or he wouldn't be here. But I think we were just trying to be ready for the fastball and, you know, ran into it," Fielder said during the broadcast. "He's too good to try to look for stuff. He's just too good, so you've just got to react."
Those were the first runs Kershaw has allowed in an All-Star Game. Going into this year's Midsummer Classic, he had pitched a combined four scoreless innings in appearances from 2011 to 2014.
Greinke and Kershaw became the first Dodgers teammates to allow at least one run during the same All-Star Game since Odalis Perez and Eric Gagne did so in 2002.
Starting left fielder Joc Pederson, who nearly won Monday's Gillette Home Run Derby presented by Head & Shoulders, went 0-for-2.
Pederson, who finished second to Todd Frazier of the Reds in the Derby, struck out against Astros lefty Dallas Keuchel to end the second inning and then did the same against Chris Archer of the Rays in the fifth, taking a big swing on a slider on the outside corner.
"I was just excited to be out there. You look around and see superstars everywhere. This was a special opportunity," Pederson said of his first All-Star Game.
Adrian Gonzalez entered the game in the seventh inning as a defensive replacement at first base and struck out in his lone at-bat, in the eighth inning, against Wade Davis of the Royals.
Yasmani Grandal followed Gonzalez and grounded out to end the inning in his lone at-bat.
Grandal did enjoy a special moment in the ninth, catching his former Reds teammate Aroldis Chapman to become the first Cuban-born battery in All-Star Game history.
"I hadn't thought of [making history], but it couldn't have worked out any better," Grandal said. "I was hoping I would catch him, because I caught him in Cincinnati for a little bit, and I wanted to see what the difference was.
"It was much easier to catch him today than it was a couple of years back."