Salvador Perez and Billy Butler also connected for the Royals, who have 14 homers in their last seven games. Gordon has nine home runs this season, three in this four-game series that concludes Sunday afternoon.
The game started at 10:14 p.m. and spilled into Sunday morning, finally ending at 1:13 a.m.
Mendoza (6-8) gave up three runs and seven hits over six-plus innings in his first appearance against the Orioles since 2008. Two of his 12 career wins have come against
Chris Tillman (5-2) allowed six runs and six hits, including three homers, in 5 2-3 innings.
Coming in, Tillman yielded only two home runs in 34 innings this season. In his only previous start against the Royals, in July 2009, Tillman also surrendered three home runs.
Playing in his third major league game, Baltimore third baseman Manny Machado went 1 for 4 with an RBI double. It was another solid outing for the 20-year-old, the first player in modern baseball history (since 1900) to have two homers and a triple in his first two games, according to information provided to the Orioles by the Elias Sports Bureau.
Adam Jones had two hits for the Orioles, who lost for the second time in eight games.
After a delay of 3 hours, 9 minutes, Gordon hit Tillman's third pitch into the left-field seats. It was Gordon's fourth leadoff homer of the season, the second in this series.
Lorenzo Cain led off the second inning with a single and Perez followed with his eighth home run, the second in two nights.
Butler homered on a 3-0 pitch in the third to make it 4-0. Butler's career-high 24 home runs are the most by a Royal since Carlos Beltran hit 26 in 2003.
Kansas City got two runs in the sixth. After Eric Hosmer hit an RBI single, Jeff Francoeur was credited with stealing home when Orioles catcher Matt Wieters threw wildly trying to get Hosmer at second on a double-steal.
Gordon homered off Miguel Socolovich leading off the seventh. Gordon's only previous two-homer game was against Minnesota in 2007.
Baltimore chased Mendoza in the bottom half. Following a walk and a single, Machado bounced a double inside the third base line before Omar Quintanilla singled in two runs. But with runners at second and third and two outs, Jones grounded out.
NOTES: The Orioles unveiled a statue of slugger Eddie Murray in the picnic area beyond the bullpen area in center field. Murray is the fourth of six Orioles Hall of Fame stars to be honored with a sculpture during the 20th anniversary of Camden Yards. Statues of Earl Weaver, Jim Palmer, Frank Robinson and Murray have already been put in place, and those of Cal Ripken and Brooks Robinson will be unveiled in September. ... Royals OF Jarrod Dyson didn't start after spraining his left ankle Friday night. KC manager Ned Yost said Dyson was day to day and could have been used in an emergency. ... Jones was hit by a pitch for the 10th time, most on the team.