C.J. Wilson (6-3) allowed a run and four hits in 6 1-3 innings, striking out three and walking four. Wilson also hit two batters, including leadoff man Nori Aoki with his 105th and final pitch. Aoki had two singles and a double.
The Angels won for the 11th time in 14 games and are a season-best seven games over .500.
Danny Duffy (2-4) gave up five runs and nine hits over six innings in his fourth start since he began filling in for Bruce Chen, who has a sore back. The 25-year-old left-hander was coming off a 1-0 victory against Baltimore.
Angels reliever Sean Burnett made his first big league appearance since May 26, 2013, after undergoing surgery on Aug. 7 to repair in his left elbow. He retired Eric Hosmer on a grounder to second base for the final out of the eighth inning.
The Angels took a 2-1 lead in the second when Iannetta hit his fourth homer of the season with one out and No. 9 hitter Collin Cowgill hit a two-out RBI single.
Trout, who sat out his first game of the season on Wednesday because of a sore left hamstring, gave Wilson a little more breathing room with his ninth home run leading off the third. The Angels extended the margin to 5-1 in the sixth on Eric Aybar's RBI single and a run-scoring double by Grant Green.
The Royals were trailing 3-1 in the fifth when Aoki led off with a double. He tried to tag up on Hosmer's one-out flyball to center and was thrown out as Freese took Trout's throw on the fly and slapped the tag on Aoki.
Alex Gordon, who leads Kansas City with 25 RBIs, opened the scoring with a two-out run-scoring single. A walk to Danny Valencia loaded the bases, but Cain took a third strike from Wilson - making him 0 for 4 in those situations and the Royals 6 for 27.
NOTES: In his six starts at the ''Big A'' this season, Wilson has allowed only one home run - a solo shot by Seattle's Brad Miller on April 1. ... Angels hitting coach Don Baylor, who hasn't been in uniform since breaking his right leg while catching a ceremonial first pitch from Vladimir Guerrero on opening night, stopped by the ballpark and said his rehab is progressing well. But he hasn't seen a tape of the incident. ''It's something I'm not going to look at,'' said Baylor, whose is hoping to return to the dugout and the batting cages sometime before the All-Star break. ''I was always a second-half player, and now I'm going to be a second-half coach. These are my guys, and I feel like I can make a contribution.'' ... Burnett was coming off a six-game rehab assignment with Double-A Arkansas. OF/IB Efren Navarro was optioned to Triple-A Salt Lake to make room for him on the 25-man roster. ... This was the fifth time since Iannetta and Wilson became teammates in 2012 that Iannetta homered when they were batterymates. Wilson is 5-0 in those games. ... Duffy recorded his 12th pickoff since the start of the 2011 season when he caught Freese leaning too far off first base in the third.