However, he didn't fare well in two outings versus New York since his one season with the Yankees in 2011.
Making his first start at Yankee Stadium since leaving the Bronx, the veteran right-hander looks to start 4-0 while trying to end his recent struggles against one of his many former teams Saturday.
Colon (3-0, 3.38 ERA) went 8-10 with a 4.00 ERA in 29 games - 26 starts - for New York in 2011. Oakland then signed him prior to the 2012 season and he went 10-9 with 3.43 ERA in 24 starts before he was suspended 50 games for testing positive for testosterone in August.
Though Colon enjoyed a solid season in 2012, he went 0-1 with a 7.11 ERA in two home starts against the Yankees.
Oakland (17-13) hopes that changes as it tries to improve to 6-0 with him on the mound. Colon, who turns 40 later this month, also looks for a better effort after he posted season highs with five runs and nine hits in six innings of a 9-8, 10-inning win over Baltimore on Sunday.
"It doesn't really matter what else goes on when you get seven shutout innings from your starter in this ballpark and you've got a fresh bullpen behind you," Oakland manager Bob Melvin told MLB's official website.
Lowrie, who has posted consecutive three-hit road games, is batting .341 in 14 career contests at Yankee Stadium.
Grant Balfour got the final out for his fourth save of the season and 23rd in a row, including the playoffs, since blowing one April 29, 2012.
"You're not going to be able to get them every night," New York outfielder Vernon Wells said. "I think you just want guys to try to have good at-bats. Sometimes the outcome is out of your hands, but it's just guys continuing to keep the same approach. We'll continue doing that day in and day out."
New York's Robinson Cano is batting .322 this season and .429 (6 for 14) with two doubles and a homer versus Colon. Teammate Ichiro Suzuki is 6 for 13 in the last three games and hitting .341 with two home runs against him.
Phil Hughes (0-2, 4.67) will try a sixth time to earn his first win when he takes the mound for the Yankees on Saturday. The right-hander has allowed two runs in three straight starts, most recently Sunday over six innings when he struck out a season-high nine in a 3-2 win over Toronto.
Hughes, who is 2-1 with a 6.00 ERA in five starts versus Oakland, has allowed 13 runs and 16 hits in seven innings without a decision in his last two against the A's at Yankee Stadium.