Ryan Braun had a solo shot, helping Milwaukee to lead 6-3.
The Reds trailed 6-3. Cincinnati loaded base with none out, but Axford fanned Jay Bruce and got Jonny Gomes to hit the victim flew into the center.
Hernandez hit an opposite-field homer into the Brewers bullpen. The Reds tied for the most-second win in their last at-bats while taking the NL Central title.
The Brewers had designs on overtaking NL Central champions after a change manager - Ron Roenicke took over for Ken Macha - and add Zack Greinke and Shaun Marcum.
The first pitch 41 degrees made for opening the second coldest in nine-year history of Great American Ball Park, pushing the 42,398 fans to bundle in coats and blankets. Volquez warming red hooded sweatshirt. Brewers fall to start the majors' most sizzling in decades.
When Gomez homered into the upper deck two field later, the Brewers became the first team in the majors to start the season with a pair of homers since Cincinnati Pete Rose - who watched from seats behind home plate on Thursday - and Bobby Tolan connected off Don Drysdale in 1969. Drysdale did not allow another run in that one, winning 3-2.
Drew Stubbs and the National League MVP Joey Votto hit solo homers, but the Reds went into their last at-bat before Hernandez ended with a three-run shot, hitting all four of the game.