Hendriks, who picked up his first big league win in 18 tries in his previous start, couldn't replicate his success against New York's high-powered offense. The rookie gave up six runs on eight hits over 6 1/3 innings to fall to 1-8 on the year.
"I think tonight you saw what happens when you leave too many balls over the middle of the plate -- they end up flying an awful long ways," Twins manager Ron Gardenhire said. "It's pretty much what hurt Liam all night long."
Nick Swisher, Curtis Granderson, Raul Ibanez and Eric Chavez all went deep for the Bronx Bombers. Hendriks became the first Twins pitcher to give up four homers in a game since Nick Blackburn did so against Detroit on Aug. 20, 2010.
"They swung the bats really well tonight and took advantage of the pitches I left up," Hendriks said. "I looked at the video, and all four home runs were in the same spot -- one changeup and three fastballs -- up and away."
Swisher was the first to go deep, crushing a two-run drive in the first inning after Robinson Cano brought home a run with an RBI groundout.
Granderson connected on his 40th homer of the year in the fourth inning before Ibanez and Chavez added solo shots of their own in the seventh.
The support was more than enough for veteran left-hander Andy Pettitte, who tossed six scoreless innings. Pettitte, who was on a limited pitch count in his second start since coming off the disabled list due to a fractured left fibula, scattered seven hits and a walk.
"It's impressive what he's doing," Yankees manager Joe Girardi said of Pettitte. "I know Andy's determination. I got a chance to see it firsthand in 1996, when he was just a kid, and how he focuses. When he wants to do something, he does it. But it's still impressive."
The Twins did have scoring chances against Pettitte, especially early in the game, but couldn't come through. Minnesota loaded the bases with one out in the first, but Justin Morneau struck out looking and Ryan Doumit grounded out to end the potential rally.
It was more of the same in the fourth, when Doumit doubled with one out but was thrown out at home to end the inning on a single to center field from Jamey Carroll.
"It's a tough play," Girardi said. "Swish was trying to cut it. Russell [Martin] picks it and puts on a quick tag. It's a big play in that game."
Minnesota didn't score until the eighth inning, when Pedro Florimon connected on his first career homer, a solo drive on a 3-2 fastball from reliever Cory Wade.
With two outs in the bottom of the ninth, pinch-hitter Chris Parmelee pulled Minnesota within three runs with a two-run triple off David Robertson, but it wasn't enough.
"It was a nice little effort at the end to get back in the ballgame -- a nice one from Parmelee," Gardenhire said. "But Liam just had too many in the seats, and we got into a little bit of a hole there. He's got to do better than that, and that's what we've said all along."