Pederson hit a solo shot in the third inning, and his two-run blast in the fifth tied it at 3. It was the 16th multihomer game of Pederson's career, and he doubled his season homer total to four.
The leadoff-hitting left fielder also doubled and is hitting .369 in May. He had a .137 batting average in April after the longtime Los Angeles Dodger was signed as a free agent in the offseason.
''I've had a roller coaster of success over the years, and I've learned you do your best by staying out of the results because they can really drag you either way,'' Pederson said. ''You have to stay on an even keel and just trust yourself. You can't really force anything in this game. It'll tell you when it's time to do it.''
Arrieta put the Cubs in a 3-0 hole after two innings but settled down to raise his record to 3-0 against Pittsburgh in 2021. He has a 15-6 lifetime record versus the Pirates.
Arrieta (5-4) went five innings and gave up three runs - two earned - on five hits with seven strikeouts and one walk.
''In the first inning, I just made some mistakes, elevated some pitches in the strike zone and they were able to take advantage of that,'' Arrieta said. ''I gave up two in the first, one in the (second), then it was a matter of minimizing the damage. Then the bullpen was lights out again.''
Four Cubs relievers combined for four scoreless innings, with Craig Kimbrel working the ninth for his 10th save. The bullpen has allowed only one unearned run over its last 29 2/3 innings.
Kimbrel gave up a leadoff double to Cole Tucker but retired the next three batters. He moved into a tie for 11th place on the MLB all-time saves list with Troy Percival with his 358th.
''Right now, we've got a good game plan, a good mentality and we're attacking guys and getting them in swing mode,'' Kimbrel said of the relief corps.
Chicago won for the seventh time in nine games and is 14-7 in May. Pittsburgh lost again in its first game back home following a 1-5 road trip.
Both of Pederson's longballs came off rookie Cody Ponce (0-1), who was recalled from Triple-A Indianapolis earlier in the day to make his first start of season and fourth of his career.
Ponce allowed four runs in five innings while taking the rotation spot of Trevor Cahill, who was placed on the injured list last weekend. The Cubs got nine hits off Ponce, who struck out two and walked one.
''He responded well,'' Pirates left fielder Ben Gamel said. ''He gave us an opportunity to win the game and that's really all we can ask for.''
Cubs second baseman Nico Hoerner left the game in the sixth inning with a strained left hamstring after going 2 for 3. He was injured when he hit the first base bag awkwardly with his left leg while trying to bunt for a hit.
Chicago manager David Ross did not have an update on Hoerner after the game but said, ''you guys saw it, it didn't look good.''
After Pederson tied the game, the Cubs went ahead in the fifth inning when Javier Baez hit a two-out double and scored on Anthony Rizzo's single.
The Pirates scored twice in the first inning on a passed ball by rookie C.J. Higgins and an RBI single by Jacob Stallings. Gamel singled in Will Craig, who doubled, in the second inning to make it 3-0.
Gamel went 2 for 2 with a double and walk before leaving for a pinch hitter in the seventh inning.
Cubs: C Willson Contreras (bruised left wrist) was held out after being hit by a pitch Sunday night at St. Louis. X-rays taken Monday were negative and Contreras participated in batting practice before the game. Contreras is expected to play Wednesday night . INF/OF Matt Duffy (low back strain) was placed on the 10-day IL retroactive to Sunday. INF Patrick Wisdom was selected from Triple-A Iowa. RHP Jason Adam was designated for assignment three days after undergoing left ankle surgery.
Pirates: RHP Chad Kuhl (right shoulder discomfort) made a rehab start for Indianapolis on Tuesday night and gave up one run and one hit in 3 1/3 innings against Omaha with four strikeouts and two walks. ... Rookie 3B Ke'Bryan Hayes (left wrist sprain) went 3 for 6 with a double and a home run in his two rehab games for Indianapolis.
The Pirates optioned RHP Kyle Keller to Indianapolis to open a roster spot for Ponce. Keller made three relief appearances for Pittsburgh and gave up three runs in 3 1/3 innings.
Cubs RHP Trevor Williams (2-2, 5.97 ERA) starts against rookie Pirates RHP Wil Crowe (0-2, 4.91) on Wednesday night. Williams is 0-1 in two starts this season against the Pirates, who released him last December, and has allowed seven runs in 7 1/3 innings. Crowe will be looking for his first career win in his ninth start and 10th appearance.
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