A win for the Rays would tie the fourth-longest home series winning streak in American League history.
"You can look at it in a negative way, that we have struggled here," Blue Jays catcher J.P. Arencibia said. "Or you can say there's no more struggling here. It's time to re-write that history. It's time to change."
James Shields, 6-2 with a 3.77 ERA, will look to finish off Toronto, who he will see for the first time this season. Shields dominated the Blue Jays in 2011.
The right-hander went 3-0 with a 0.71 ERA over 25 1/3 innings last year, but has struggled against Blue Jays slugger Jose Bautista.
Bautista, who has eight home runs in May and two three-hit games in his past three, has two homers and a .971 OPS against Shields over 21 career at-bats.
"I don't really look at his numbers," Shields said of the two-time defending home run champion. "He's always a threat when he gets up to the plate. Right now, he's doing pretty good, so it's our job to stop that."
Toronto, meanwhile, will turn to ace Ricky Romero as the club looks for its first series victory over Tampa Bay since August 2010.
Romero, coming off a career year in 2011 where he won a personal-best 15 games and had his lowest ERA in three seasons at 2.92, has struggled despite losing just one game in nine starts.
"I think coming off a very strong year in 2011, it just goes to show you, no matter how much success you have had, there is always maintenance work required and he is in the midst of doing that right now," Blue Jays manager John Farrell said about his lefty. "Yet, while he hasn't pitched as sharp over a period of time here as he did a year ago, he still sits here at 5-1 and keeps us in the ballgame."
The biggest thing plaguing Romero has been his command. Romero has allowed 14 walks in his last three starts and has the lowest strikeout to walk ratio of his career at 1.40. He did beat the Rays earlier this season at Rogers Centre and has held opponents to a stingy .216 batting average.
Romero is holding this current version of the Rays to a .192 average and .647 OPS over 167 career at-bats.
Rays: Lineup switch pays off for Maddon
Rays manager Joe Maddon unveiled a different lineup for Tuesday's contest against Toronto.
The skipper had Carlos Pena batting out of the leadoff spot, while shifting Ben Zobrist to cleanup. It marked the seventh different spot in the order that Pena has hit this season, but the power-hitting first baseman had no problems with the unlikely move.
"It's very powerful when you're able to utilize your resources in many different ways, and Joe is very good at that, maybe the best I've ever seen," Pena said.
Pena rewarded Maddon by going 2-for-5 with a massive three-run home run off Drew Hutchison in the fourth inning of Monday's contest that traveled an estimated 456 feet.
Zobrist went 1-for-4 with a run scored and made the first error of his career in the outfield.
Fernando Rodney collected his 14th save in 14 opportunities in Tampa Bay's 8-5 win over Toronto on Tuesday.
The right-hander, who lowered his ERA to 0.44, has not allowed an earned run since April 19, against the Blue Jays.
Blue Jays: Hot start to Gomes' career
Yan Gomes has made the most of his opportunity with the Blue Jays since making his Major League debut May 17 against the Yankees.
The rookie is batting .357 and hit his second career homer in Tuesday's loss to Tampa Bay. Gomes has hits in four of the five games he's played to go along with four RBIs and four runs scored.
Gomes, who was filling in at third base while Brett Lawrie served a four-game suspension, started at first on Tuesday, while Edwin Encarnacion was the designated hitter.
Farrell said that Gomes could stay in the mix and up with Toronto because of his versatility, as he also played catcher in the Minors, too.
Toronto added Gomes to its 25-man roster after optioning Adam Lind to Triple-A Las Vegas.
Kelly Johnson has reached base safely in 17 consecutive games dating back to May 5 after walking in the fifth inning on Tuesday.
The Blue Jays second baseman has reached base in every game except one since Farrell moved Johnson into the leadoff spot May 2. Johnson had previously been hitting in the two-hole, but swapped spots with shortstop Yunel Escobar.
Besides Gomes, who has just 14 at-bats, Johnson's .356 on-base percentage is tops on the team.