Machado was called out in the sixth inning after dropping his bat near Murphy while the Diamondbacks catcher tried to catch a popup, a disputed decision that led to Padres manager Andy Green's ejection.
Machado might have brushed Murphy as he spun out of the box and looked up at the ball while Murphy moved to catch the popup about 10 feet down the first base line. As he ran by, Machado tossed down his bat near Murphy's feet, though the bat did not touch Murphy and was not in his path. The catcher dropped the pop foul, but plate umpire Bill Welke signaled for interference and called Machado out.
The catcher had a clear read but then lunged slightly at the last second and moved his head as the ball popped out of his glove.
Green came out to argue with Welke and was ejected. Green slammed his cap to the ground.
Asked if he made contact, Machado said: "Not that I was aware of. Honestly I didn't even know what was going on until Andy came out there and started arguing. I had to ask him, was I out, was I safe, and he was like, `Uh, I don't know.' At that point I went back to the batter's box.
"I hit the fly ball, looked up, saw it, put my head down and went to go run," Machado added. "I don't even think I touched him. He even said no. Things happen on the ball field. I mean, as a player we don't feel, I don't think I hit him. Maybe we'll see the replay and maybe I did. Who knows? I don't know. I didn't see the replay yet. As I was aware of I don't think I touched him though."
Machado has been criticized in the past over his baseball ethics. He was called a "dirty player" by NL MVP Christian Yelich during last year's postseason after stepping on Brewers first baseman Jesus Aguilar's leg while running out a groundout.
Green said he had no idea how Welke interpreted the play.
"If you put it in super slow-mo you might be able to see a heel-click," Green said. "If he saw that, that's really, really, really impressive. A graze of the heel."
Welke told a pool reporter that it doesn't matter if there's contact and that Machado was ejected for "what was going on at home plate. ... The minute the batter makes contact with the ball, he's no longer the batter, he's the batter-runner. The batter-runner has to give way to a fielder making a play on a batted ball. . It doesn't matter if it's intentional or not. A runner always has to give way to a fielder making a play on a batted ball."
Green said the bat drop "had no bearing on the play."
Fans booed Welke for the rest of the game.
"On that play my mind was obviously on catching the ball, so I'd be lying if I said that I felt anything out of the norm," Murphy said. "Watching the video I can see that maybe we did brush up against each other. I don't know if my foot hit the bat or not. In the moment it didn't feel like it affected being able to catch the ball."
Greinke became the first pitcher with a multihomer game and 10 or more strikeouts since Madison Bumgarner did it for San Francisco at Arizona on opening day 2017. Bumgarner's first homer that day was off Greinke.
Greinke stunned left-hander Eric Lauer (1-1) and the Padres with a three-run, 413-foot shot to straightaway center field with one out in the fourth to give the Diamondbacks a 4-2 lead. He then hushed the crowd at Petco Park when he homered again off the lower balcony on the Western Metal Supply Co. Building in the left field corner in the sixth.
His second homer followed Murphy's monster shot off the railing on top of the four story brick warehouse, his first.
Greinke's homers were his first since hitting two during the 2015 season while with the Los Angeles Dodgers. He has eight in his career. His four RBI are a career high.
"First one felt really good," he said. "I haven't had a ball that far in a while so that was nice."
He got the silent treatment in the dugout. "It was the first time I wanted anyone to talk to me all year and they didn't want to talk to me then," he said.
Greinke allowed Renfroe's two-run homer with two outs in the first. He allowed two singles to open the second and then retired the next 13 batters, including striking out the side in the fourth.
The right-hander allowed three runs and six hits while walking none. Greg Holland pitched the ninth for his second save in two chances.
On opening day, Greinke allowed four home runs and seven runs on seven hits in 3 2/3 innings of a 12-5 loss at the Los Angeles Dodgers.
After Machado was called out and Green ejected, Renfroe followed with his second homer to pull the Padres to 6-3. It was his sixth career multihomer game.
Walker's homer in the seventh, his third, gave the Diamondbacks a three-run lead before Myers hit a pinch, two-run homer in the bottom of the inning.
Padres rookie shortstop Fernando Tatis. Jr. made a twisting, turning, leaping, tumbling highlight reel catch of Greinke's poke to shallow left to end the second.
Diamondbacks: LHP Robbie Ray (0-0, 5.40) is scheduled to start the series finale Wednesday afternoon.
Padres: LHP Joey Lucchesi (1-0, 0.00) gets the start for San Diego.
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