This one was worth the long wait.
"It couldn't come at a better time than today," Nieves said. "It was awesome just to contribute with my bat today."
Nieves also got the first curtain call of his career from the crowd of 40,184, which saw the Padres win their third straight in the four-game series.
Nieves was a 47th-round draft pick of the Padres in 1995. He made his big league debut on July 21, 2002, when he caught Peavy and got his first hit, a single off Arizona's Randy Johnson.
After a roundabout journey that included stints with six other big league clubs and numerous minor league teams, he signed a minor league contract with San Diego in January.
"The only thing I can control is my attitude," he said. "I worked really hard in the offseason to be in good shape so whatever team I signed with, I wanted to be my best."
With Derek Norris given a day off after catching six straight games, Nieves got his first start. He homered to left on a 1-1 pitch with two outs in the fourth. Peavy (0-1), whose first start of the season was delayed because of a back injury, loaded the bases on a single by Kemp, a walk to Justin Upton and a one-out single by Will Middlebrooks.
"I know my No. 1 job when I'm catching is just to call a good game. To contribute with the bat is a plus," Nieves said. "It's been a while since I've had an at-bat but I've been working really hard."
Nieves said he still loves baseball despite bouncing around the majors and minors.
"A lot of stuff happened to me in my career that I don't think I deserved, but I'm doing what I love and not a lot of people can say that. Once again I'm blessed I can put a uniform on one more year and hopefully, I want to play, three, four more years," he said.
Peavy said the cut fastball to Nieves "came right out of the top of my hand and just didn't do much.
"It was just that one pitch," Peavy said. "You could go back and look at the game and there it is, the one pitch. I wasn't sharp by any means in that inning but we got soft contact. I just wasn't able to avoid a couple of outs and made a bad pitch to Nieves, obviously."
Peavy, the unanimous 2007 NL Cy Young Award winner while with the Padres, allowed four runs and four hits in four innings, struck out five and walked three.
San Diego's Tyson Ross (1-0) allowed three runs and five hits in six innings, struck out eight and walked four. Craig Kimbrel pitched the ninth for his second save in as many chances.
The Giants had given Peavy a 2-0 lead on Matt Duffy's RBI single in the second and Brandon Belt's RBI hit in the third. Belt had missed four games with a strained right groin.
Gregor Blanco's RBI triple down the right-field line in the sixth pulled the Giants to 4-3 before Alexi Amarista's RBI triple into the left-field corner in the bottom of the inning gave the Padres a two-run lead.
The series drew 168,171 fans, the highest attendance for a four-game series since Petco Park opened in 2004.
Giants: 3B Casey McGehee said an MRI showed he has a bone bruise in his left knee. He had a cortisone shot and is expected to be out a few days. "All things considered I feel real fortunate. It's as good of news as I could hope for," McGehee said. He said he suffered the injury Monday against Arizona and aggravated it during an at-bat in the first inning Saturday.
Giants: RHP Chris Heston (1-0, 0.00 ERA) will become the second rookie in San Francisco history to start a home opener when he faces Colorado on Monday. The Rockies counter with Eddie Butler (0-0, 3.18)