Coco Crisp followed with a single and a score to extend on the Red Sox's lead, but it was Varitek's homer that proved to be a huge shift in momentum.
"That's the type of guy you don't expect to hit home runs off you," Shields said of of Boston's No. 9 hitter, who snapped an 0-for-15 slump with the blast. "So, you kind of got to be aggressive a little bit and he got a great bat on it."
Varitek also got a great pitch. Down 2-0 in the count, Shields admitted he was just trying to get a called strike on the Red Sox's captain, given that the usually economical pitcher had already issued three walks.
"Our team did a great job of getting ahead early," Shields said. "And I gave up the home run to [Kevin Youkilis] and we tied it up, and then I gave up the home run to Varitek. So, I didn't do a very good job of [keeping the lead]. And I think that's when the momentum changed."
He wasn't the only one.
Boston's manager Terry Francona said he couldn't think of "anything more appropriate" at that moment than Varitek's homer, as the Red Sox dugout erupted in cheers.
"We'll take runs any way we can get it," Francona said. "But by that means and by who hit it, it was not just a big run. It was a huge run."
And it was one the Rays couldn't get back.
Shields exited following Crisp's single with two out in the sixth inning, and Tampa Bay -- which scored previously on homers from B.J. Upton and Jason Bartlett -- had no rebuttal to Varitek's blast.
"Shields did a great job of keeping us right there," Rays third baseman Evan Longoria said. "That's a tough ballclub over there and they are going to match us blow for blow."
But Shields, the Rays' most consistent and competitive starter, didn't see it quite the same way. He's earned the "Big Game" James moniker because he has so often produced at times the Rays need him to step up and go deep in games.
"I was just a hair off," said Shields, who particularly struggled with command of his fastball, a critical pitch in setting up his devastating changeup. "Felt like I was just missing. That's why they call it a game of inches."
Shields threw 65 of his 109 pitches for strikes, but his tendency to get behind in the count caused his pitch count to hover around 60 after just three innings.
The right-hander lasted 5 2/3 making his shortest stint -- minus a one-inning tune-up on Sept. 28 -- since Aug. 14's no-decision in Oakland.
But despite the loss -- just his fourth at home this year -- Shields was confident in the Rays' rebound abilities for Sunday's Game 7.
"We just got to stay positive," Shields said. "We got one more game, and now it's do-or-die. We got to find out what we are all about."