With the loss, the Royals are just a half-game up on the last-place Twins in the American League Central.
Guthrie, acquired on Friday in a trade with the Rockies, ran into trouble early on -- allowing a solo home run to Ryan Doumit in the second inning, the first of two on the day for the Twins designated hitter. In the third, Guthrie issued back-to-back one-out walks after a Jamey Carroll single to load the bases. He retired Josh Willingham on a popout to shortstop for the second out, but Doumit followed with a double through the left side of the infield to plate two runs.
Brian Dozier followed with a two-run double off the left-field wall, pushing the Twins' lead to 5-0.
"I think the biggest mistakes were the walks in that one inning," Guthrie said. "I had Joe [Mauer] down 0-2 and couldn't finish him off and ended up walking him. For the most part, the pitches they hit were pitches I executed. But I got myself in trouble by not executing pitches before that in those at-bats.
"You want to go out there and limit the runs, and give your team a chance to win, which after the third inning really wasn't there. You look at the pitches that scored the runs, both of the two-run hits, I threw the pitches for the most part what I was trying to do, and the hitters did a better job."
Despite the poor results, manager Ned Yost was pleased with the way Guthrie pitched in his first Royals outing.
"I thought he threw the ball OK," Yost said. "He had the rough third inning where they scored some runs, but there was never a pitch that I thought was a horrible pitch. I thought they all hit pretty good pitches. I was very impressed with his ability to pitch down in the zone and keep the ball down. I don't think he elevated five pitches all day. From that point of view, that's very encouraging."
Doumit's second-inning homer was the 22nd allowed by Guthrie this season -- making it four straight games in which he's surrendered a home run. He also issued three walks and threw 91 pitches in his five innings. It was the most walks he'd issued in a game since allowing four on May 15 at San Francisco. Guthrie is now 0-7 since his last win on May 31 against Houston.
Though they did fall behind early, the Royals made a game of it with a few late-inning rallies. Trailing 7-1 in the bottom of the seventh, the Royals nearly had a bases-loaded opportunity, but Chris Getz was called out at second base on a ground ball hit by Alcides Escobar.
Getz and Yost disagreed with the call and exchanged words with second-base umpire D.J. Reyburn.
The play loomed larger when the Royals pulled within two runs by scoring twice in both the eighth and ninth innings, highlighted by home runs from Billy Butler and Yuniesky Betancourt. The frustration boiled over, and Escobar and Yost were both ejected following the top of the ninth for again arguing with Reyburn.
"In hindsight, it was a big play, because we would've had bases loaded, middle of the lineup coming up and we end up losing by two runs," Getz said. "Who knows what would've happened that inning? Clearly I thought I was safe. Esky thought I was safe. Most people thought I was safe. But [Reyburn] made that decision, and it was too bad."
Twins starter Samuel Deduno held the Royals in check for most of the afternoon. The right-hander picked up his first Major League win, going 6 1/3 innings and allowing just six hits in his third big league start.
"He was really funky," Getz said. "He was changing speeds with his fastball. His ball was cutting, it was running. It was the first time we've faced him. He wasn't really pitching off his fastball. He was just throwing a lot of offspeed [stuff]. And to be honest, he was locating really well from what I could tell. He pitched well and deserved to win."
The Royals finished 3-7 on the homestand following the All-Star break and are now 5-15 in their last 20 games. They haven't won a series since sweeping the Tampa Bay Rays on June 25-27.
Kansas City heads to Anaheim, where it will begin a seven-game road trip on Monday night against the Angels.
"For some reason, we haven't played really well on long homestands. We had the long homestand at the beginning of the year and didn't play well," Yost said. "We're not winning games. We need to find ways to win more games here. It will be kind of good to go to a little bit cooler climate and see if we can get our feet underneath us, and come back on a roll."