Just three pitches later, Jason Kipnis homered to straightaway center field as the middle infielders went back to back. The homer was Kipnis' third of the spring.
Tyler Naquin has been one of the Indians' best performers this spring and kept up that trend Wednesday. The outfielder continued to show he is deserving of a spot on the Opening Day roster as he doubled and hit a pair of solo homers in the game.
"He has done a really good job," Indians manager Terry Francona said. "He's never been lacking strength. I don't care what ballpark he's in, both those balls, they're hit really well. I'm sure it's doing a lot for his confidence."
Cleveland raced to an early lead, but the Royals stormed back with a six-run third, which included a stretch where six straight batters reached base and scored.
Mike Moustakas continued to swing a hot bat as he hit his second homer of the spring, a solo shot, to jump-start the scoring.
Before Wednesday, homers hadn't been an issue for Medlen this spring. Wednesday's outing, in which he allowed all four home runs, was the fourth of the year for the right-hander, who had given up just one long ball over his first three starts.
Medlen left after 3 1/3 innings. He gave up seven hits and five earned runs.
"His secondary stuff was good," Royals manager Ned Yost said. "He just battled with command a little bit. He had a really good curveball today and a good changeup. He got his work in."
Yost also noted that several players struggled with the high sun and windy conditions Wednesday.
"Sun is always tough here," he said. "Kind of typical Arizona game. You just battle it."
The Royals jumped all over Cleveland's Danny Salazar, who lasted just 2 1/3 innings and gave up six runs (five earned) on six hits and three walks.
"I think I got behind in the count a couple of times," Salazar said. "Sometimes I was ahead and I was working on my pitches, kind of threw a few up."
However, the offense bailed out Salazar as Roberto Perez drove in two with a go-ahead single in the sixth.
Up next for the Indians:Trevor Bauer will get the ball in a rare Spring Training night game Thursday. The lights will be shining bright as the 25-year-old right-hander goes up against Clayton Kershaw and the Dodgers. Bauer has made three appearances this spring -- two starts -- and has given up four runs in nine innings. The 10:05 p.m. ET game will be shown on MLB.TV.
Up next for the Royals: The Royals travel to Phoenix to take on the Brewers in a 3:05 p.m. CT start Thursday. The game will be broadcast on MLB.TV and on an exclusive free webcast . Right-hander Dillon Gee will start for the Royals, followed by right-hander Kelvin Herrera and left-handers Brian Duensing, Danny Duffy and John Lannan.
William Boor is a reporter for MLB.com. Follow him on Twitter at @wboor. This story was not subject to the approval of Major League Baseball or its clubs.