Colon makes his first start as a 40-year-old Sunday when he attempts to lead the visiting Athletics to their 11th straight victory over the AL-worst Astros.
Behind a season-high 18 hits and double-digit runs for the first time since April 30, Oakland (27-23) cruised to its seventh win in eight games with an 11-5 victory in Houston (14-35) on Saturday.
Josh Donaldson homered and tied a career high with four hits to lead the A's, who have outscored the Astros 75-37 during 10 consecutive wins in the series. The third baseman leads the team with a .322 batting average, .398 on-base percentage and 30 RBIs.
"He went through one little period where he was down some, but he's been consistent all year,'' said manager Bob Melvin, whose club hasn't lost to Houston since June 12, 2007.
Now Oakland looks to complete a three-game sweep with Colon (4-2, 4.31 ERA) on the mound.
After going 0-2 with an 8.22 ERA during a three-start stretch, the right-hander has given up five runs and 10 hits over 13 innings in his last two outings.
Colon won for the first time in nearly a month after allowing two runs and six hits over seven innings in a 9-2 victory at Texas on Monday.
"I mean, he's 40 and we'd like to try to get him through a season,'' Melvin said of Colon throwing 95 pitches. "So anything over 100 for me is starting to get a little uncomfortable for me.''
Colon has already beaten Houston twice this season, yielding four runs over 12 innings in two April outings. He's 5-2 with a 3.42 ERA in eight career starts against the Astros.
This time, he faces a Houston team that has batted .219 with runners in scoring position while losing three of five on its eight-game homestand.
Jason Castro went 3 for 4 with two homers and three RBIs Saturday and is 3 for 6 with a homer against Colon this season.
Matt Dominguez has hit three homers in the first two games of this series, giving him seven over his last 12 contests.
"He's really tapping into what we always knew was in there,'' manager Bo Porter said. "The pull power is definitely there, and he has proven to the league that he can make adjustments."
Scheduled Houston starter Dallas Keuchel (1-1, 4.93) makes his fourth start since replacing the ineffective Philip Humber in the rotation.
While the left-hander hasn't been sharp with six walks and 16 hits allowed in his last two starts spanning 12 1-3 innings, Keuchel did earn his first victory in a 6-5 win over Kansas City on Monday. He yielded four runs and nine hits with four walks and a season-best six strikeouts in 6 2-3 innings.
Seth Smith went 3 for 5 on Saturday and is 2 for 3 with a home run against Keuchel, who has given up one run and six hits over six innings of relief against the A's this season.
Houston native Chris Young continues to hit well at Minute Maid Park, going 6 for 10 with a homer and five RBIs in the first two games of this series to raise his average to .429 in 20 career games there.