Starlin Castro went 3 for 4 with two doubles for the Cubs, who have won two of three following a four-game losing streak.
Brayan Pena hit a solo homer for the Reds, who have lost four of five.
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Edwin Jackson (2-2) beat Cincinnati for the second time this year, allowing four runs and five hits in 5 2-3 innings. Brian Schlitter, Wesley Wright, Neil Ramirez and Hector Rondoncombined for two-hit relief.
Schierholtz added a two-run single off Sean Marshall against a drawn-in infield in a four-run ninth.
Chicago needed just three batters to take a 2-0 lead in the first on Emilio Bonifacio's leadoff single and Rizzo's 426-foot, opposite-field homer to left-center.
Todd Frazier tied the score with a two-out, two-run double in the half.
Pena, signed by the Reds as a free agent in November, gave the Reds a 3-2 lead when he homered leading off the second - his first home run since Aug. 11. His previous NL homer was for Atlanta against the Marlins on April 13, 2007.
Castro's single tied the score in the third.
Cincinnati starter Tony Cingrani gave up three runs and six hits in four innings.
Brandon Phillips had an RBI single in the fifth, his eighth hit in his last 46 at bats (.174).
Reds manager Bryan Price confirmed that LHP Aroldis Chapman will start and pitch one inning for Class A Dayton on Thursday in the first game of his minor league injury rehabilitation assignment. Price expects Chapman to make four appearances over seven to 10 days in the minors. Chapman had a plate inserted above his left eye to heal fractures from a line drive on March 19. ... Rizzo drew a career-high four walks. ... The Cubs are scheduled to open a five-game homestand on Friday against St. Louis. The Reds are scheduled to open a four-game home series Thursday against Milwaukee, the team with the big leagues' best record.