Guthrie limited the Rangers to six hits and three runs in six-plus innings, but it was not enough for him to pick up his first victory in more than two months.
Matt Harrison gave the beleaguered Texas pitching staff a strong start, Mitch Moreland hit a three-run homer and the Rangers defeated the Royals 5-3.
Guthrie (3-11) is winless in three Kansas City starts since being acquired in a July 20 trade with the Colorado Rockies for Jonathan Sanchez and has not won since May 31 against Houston.
"That's the best start we've seen from him," Royals manager Ned Yost said. "It was great to see him get on track. He was getting his fastball up to 95 and executing pitches.
"He kept the ball down and he really matched Harrison pitch for pitch. That's a difficult task against their lineup and Jeremy almost did that. He kept us in the ballgame; he kept us one swing away."
The Rangers loaded the bases with one out in the first on a single by Ian Kinsler and walks to Elvis Andrus and Adrian Beltre, but scored only one run. Nelson Cruz's fly ball to Jeff Francoeur at the wall in right field brought home Kinsler.
"We caught a break there on Cruz," Yost said. "In Texas that ball is out of here. It's in the seats. He gave up the second run on a curveball up just a little bit. It wasn't a horrible pitch, just a little up. He went after them."
Guthrie threw only 11 strikes in 25 pitches that inning.
"The first inning I was up in the zone a little," Guthrie said. "After that I was getting that feeling, making better pitches. I was trying to make close pitches and make the best pitches. In the first, I didn't really have the feel to make the best pitches. I just need to locate better."
The Royals tied it in the second when they loaded the bases with no outs. Salvador Perez started it with a single, Francoeur walked and Eric Hosmer beat out an infield single. Yuniesky Betancourt, however, grounded into a double play with Perez scoring.
The Rangers took the lead in the fourth, which Beltre opened with a single, advanced to second on a wild pitch and scored on David Murphy's single. Murphy is hitting .396 with 32 RBIs in 53 at-bats with runners in scoring position.
"I was surprised (Murphy) took a swing at it, it was such a bad pitch, but I made my own mess by leaving the ball up in the zone," Guthrie said.
The Royals chased Harrison in the seventh. Chris Getz and Alex Gordon had two-out infield singles. After Alcides Escobar's run-scoring single, Tanner Scheppers replaced Harrison, who held the Royals to two runs and eight hits.
Betancourt's two-out double in the eighth scored Francoeur with the final Royals run.
Alexi Ogando worked a 1-2-3 ninth for his second save in five opportunities.
NOTES: Rangers manager Ron Washington said he would not use RHP Joe Nathan on Friday and probably not Saturday after his closer threw 62 pitches in pitching an inning each Wednesday and Thursday. He gave up four runs and four hits, including three home runs, in the appearances against the Angels. It was the first time this season Nathan had allowed earned runs in consecutive games. ... 3B Mike Moustakas was held out of the Royals lineup with a bone bruise on his right knee. Moustakas aggravated it Thursday sliding into second base against Cleveland. He first hurt his knee on a fielding play in the first inning July 28 at Seattle. ... RHP Scott Feldman, who starts Saturday for the Rangers, has won five straight decisions after starting the season 0-6. The Royals will counter with rookie LHP Will Smith.