"As you saw tonight, up and down the lineup, we're capable of doing that," Hamilton said. "When you look at what he's been doing as of late, he's been throwing the ball well. So it's encouraging to know you've had good at-bats against a guy like that. It's just good to create a little bit of fuel to the fire. The guys were smiling and having fun."
Guthrie (5-1) yielded five runs and 11 hits over seven innings. He held the franchise record for consecutive starts without a loss while winning his previous 10 decisions. It was his first defeat since Aug. 3 last year, when Texas beat him 5-3 at Kansas City.
"The streak was because of 25 guys that played well behind me every time I was on the mound, and they really picked me up. That's how a streak like that happens," Guthrie said. "Tonight they tried to battle for me, and I couldn't get any momentum on our side. It was one of those nights where I didn't have a good feel and wasn't able to execute pitches."
Hamilton, who batted .212 with 11 RBIs in his first 38 games with the Angels after signing a five-year, $125 million contract in December, drove Guthrie's first pitch to him in the sixth inning far beyond the trees in center field with two outs to increase the lead to 4-2.
"I went back and looked at (some tape from) 2010 -- the end of May and early June, because I struggled the first month and a half of that season," Hamilton said. "I looked at what kind of adjustment I made then and tried to simulate that in BP today and in the game. As the game went on, I saw more pitches and felt good."
The Angels' right fielder, who was the AL MVP in 2010, made his fourth start at designated hitter after being removed from Monday night's series-opening 11-4 loss in the seventh inning because of lightheadedness caused by sinus congestion.
"It was good in Houston and it felt OK in Chicago. Today it felt better," Hamilton said. "I felt like I was seeing the ball better and had a little better pitch selection throughout the game. I felt OK while I was hitting. But like last night, once I would run, I'd kind of feel a little off. So we'll give the medicine a couple of days and see if it kind of works its way out."
Trout ended the scoring in the seventh with his seventh homer, a towering drive over the double-decker bullpen in left field. It was the first time in Guthrie's 10-year career that he allowed four homers in a game.
Jason Vargas (2-3) gave up five hits in seven-plus innings and struck out seven. Both runs against the left-hander were knocked in by the suddenly hot Billy Butler, who had an RBI double in the fourth and a homer in the sixth.
"He mixes speeds well, locates, and he just knows how to pitch," Butler said. "Over the years he's gotten better and better. He knows what he has, knows his stuff and basically knows how to approach hitters. He's a lefty and he throws in the upper 80s (mph), so you have to make him come to you and bring the ball up. That's easier said than done."
Butler opened the scoring with an RBI double. But the Angels responded with two runs in the bottom half, as Pujols launched his sixth homer over both bullpens leading off the inning and Kendrick hit his sixth of the season with two outs.
Trout made it 3-1 in the fifth with a sacrifice fly after the Angels put runners at the corners on singles by J.B. Shuck and Erick Aybar, who returned to the lineup after missing four games because of tightness in his right hamstring.
"It just shows you how fragile a streak like that is and how impressive it is," Butler said. "Jeremy's going to pitch well all year, and he's pitched well to this point. We all have confidence in him, and we know when he goes out there we have a great chance to win every time."
Los Angeles got two runners thrown out at third base by catcher Salvador Perez in the third. ... The Angels are 4-0 when Hamilton is the DH. He is 8-for-25 against Guthrie with three home runs. ... The last pitcher to give up four homers against the Angels in a game was Oakland's Dan Straily on Aug. 8, 2012, in his second big league start. ... Angels LHP C.J. Wilson will match up against LHP Chris Sale of the White Sox for the second time in six days on Friday night. Sale outpitched Wilson with a one-hitter Sunday at Chicago, beating the Angels 3-0.