Hernandez homered in the second inning for all the runs Cincinnati needed and also doubled and scored a run later.
Juan Francisco added a two-run single for the Reds, who have won two in a row since dropping the opener of this four-game series on Monday.
Cueto pitched 3 2/3 shutout innings before he was pulled because of a strained right lat muscle. He gave up three hits and a walk while lowering his earned run average to 2.31 for the season.
Sam LeCure (1-1) replaced him on the mound and threw 2 1/3 innings to earn the win despite giving up two runs on three hits.
Chicago starter Casey Coleman (2-8) remained winless for almost four months after allowing six runs on six hits and three walks in 3 2/3 innings.
Working as a reliever and a starter, Coleman is 0-5 in 10 outings since winning a 5-1 decision in Florida on May 19.
"He just didn't make enough quality pitches tonight," said Cubs manager Mike Quade. "At this point you just gotta keep working with him and hope he gets better."
Carlos Pena had an RBI double for the Cubs.
Francisco doubled and Drew Stubbs walked before Hernandez knocked a high fastball over the wall in left-center field for his 12th homer of the season.
Two of Coleman's three walks came against Joey Votto and Jay Bruce with one out in the third inning. They moved up on a ground out and scored on Francisco's line-drive single into right field to make it 5-0.
Cueto came out in the fourth and hasn't earned a decision in his last five starts, but the Reds are now 4-1 in those games.
"He threw a couple pitches, one 94 (mph) to Soriano and a great slider, but I looked at Ramon and Ramon shook his head," said Baker. "That was the sign."
Edgar Renteria added to the lead with an RBI single in the fourth, scoring Hernandez after he led off with a double. The Cubs didn't get on the board until the sixth, when Starlin Castro and Aramis Ramirez hit singles and scored on Pena's double and Soriano's ground out.
Heisey hit his 16th homer of the season off Ramon Ortiz in the eighth.
This series marked the start of a 10-game homestand for the Reds...The Cubs are 3-3 on a seven-game road trip.