Guthrie struck out a season-high seven batters to top 1,000 for his career and Perez homered for his 500th career hit to help Kansas City complete a three-game sweep of the Oakland Athletics with a 5-3 victory on Sunday.
"We had two big milestones today, which I think are big," manager Ned Yost said. "So they got that behind them and now they just keep moving forward."
Omar Infante hit a tiebreaking single in a three-run sixth inning for the Royals, who have won five of six to open a nine-game road trip.
Guthrie (6-5) allowed two runs in six innings and reached 1,005 career strikeouts in his 12th big league season.
"It's 1,000 more than I thought I'd probably ever thought I'd have," he said. "It's a great accomplishment to be able to get there and have the endurance to get to that number."
Perez took much less time to reach his big number, getting there in his fifth season with a homer in the eighth inning off Edward Mujica that provided insurance for the Royals.
"It means a lot," he said. "It's pretty special to me."
"We were playing really good ball lately and this happens," Muncy said. "It's really frustrating that we had good momentum going as a team and we were playing really good ball."
Billy Burns helped spark a two-run third inning for Oakland when he led off with a single to extend his hitting streak to 16 straight games.
Ben Zobrist drove in the first run with a sacrifice fly and Josh Reddick made it 2-0 when his popup to shallow left fell between shortstop Alcides Escobar and left fielder Alex Gordon for his 500th career hit.
A poor defensive play by Oakland helped the Royals take the lead in the sixth. With runners on first and third and one out, Perez hit a slow grounder to third base. Muncy charged and his throw home was high. Mike Moustakas scored on the fielder's choice and the runners advanced to second and third on Muncy's throwing error.
Alex Rios tied the game with a sacrifice fly and Infante gave the Royals their first lead with his two-out hit that knocked out Chavez.
"I got to stop the bleeding and make a pitch," Chavez said. "It didn't go our way. I made a pitch to the next hitter for what would have been the third out. I've still got to stop the bleeding there. There's no excuse for it. It's all my fault."
Royals: OF Lorenzo Cain did not start after tweaking his hamstring stealing a base Saturday. He pinch hit for Eric Hosmer in the eighth and singled. Hosmer, who was moved to DH from first base, sprained his left ring finger on that same double steal Saturday and left Sunday's game early. He is day to day. ... Escobar was also removed in the eighth inning for precautionary reasons with a split nail on his right index finger, but Yost said he thought Escobar would be able to play Monday.
Athletics: Burns (hip flexor) returned to the lineup after missing the previous two games.
Burns had two hits and is one game away from tying the Oakland rookie hitting streak record of 17 games shared by Mike Edwards (1978), Luis Polonia (1987) and Terrence Long (2000).
Athletics: Kendall Graveman, who is 3-2 with a 2.31 ERA in seven starts since being recalled from the minors, starts the opener of a three-game series against Colorado.