Colon and Gallardo will start opposite each other Thursday, when the A's attempt to re-establish their surge by taking two of three from the Brewers.
Colon (6-2, 3.33 ERA) is tied with Tommy Milone for the team lead in wins, and his ERA is the lowest among any of the A's starters.
The 40-year-old right-hander hasn't managed this many wins at this point in a season since 2005, when he won the AL Cy Young Award by going 21-8 with a 3.48 ERA with the Los Angeles Angels.
Colon was 10-9 with a 3.43 ERA in 24 starts with Oakland last year before he was suspended 50 games for a positive testosterone test in August, missing the playoffs for the AL West champion.
"There's still a little something in the tank," manager Bob Melvin said. "He's always out to prove that he can be a successful pitcher at the major league level and he can still pitch as a power pitcher, which he does. He'll never tell you that, but the reason that he's had the lengthy career that he's had is that he never lets down."
Colon has won three straight starts with a 0.78 ERA and carries an 18-inning scoreless streak into this game after throwing a five-hitter in Friday's 3-0 win over the Chicago White Sox.
Another strong effort may help Oakland rebound from Tuesday's 4-3 defeat to the Brewers after winning the series opener.
Colon last faced them in a win with the Montreal Expos on Aug. 9, 2002, in Milwaukee.
While Colon's re-emergence is unexpected, Gallardo's struggles have been alarming for Milwaukee.
The right-hander (4-5, 5.05) led the team with 60 wins and 815 strikeouts with a 3.68 ERA over the past four years, establishing himself as the Brewers' top starter.
That status has taken a significant hit, especially over the past month. He's 1-5 with a 5.97 ERA in his past six starts, serving up seven of the nine homers he's allowed on the season. That stretch includes going 0-2 with a 6.19 ERA in three home starts.
Gallardo snapped his five-game losing streak Friday, despite surrendering five runs - three in the first inning - and three homers before leaving with two outs in the sixth of an 8-5 win at Philadelphia.
Catcher Jonathan Lucroy, though, felt there were signs of improvement.
"I thought (Gallardo) pitched really well, considering he hasn't had his best stuff for a while," Lucroy said. "I saw some flashbacks of 'old Yo,' for sure."
Gallardo will have to contend with Yoenis Cespedes, who is hitting .333 during an 11-game road hitting streak. He had a career-high 16-game run from June 26-Aug. 10, and is 5 for 10 with four RBIs in this series after hitting two homers Tuesday.
The Brewers have won three of five, matching their total from the previous 16 games.
"We need to start winning some more games,"left fielder Ryan Braun said.
Braun is one of several subjects of an ESPN report claiming that MLB is looking to suspend players who have been linked to a Florida anti-aging clinic and its director.
"I've already addressed everything related to the Miami situation," Braun said. "I addressed it in spring training. The truth has not changed. I don't know the specifics of the story that came out, but I've already addressed it."