Upton capped a five-run third inning with a three-run homer and Tampa Bay completed a four-game sweep of the Red Sox with an 8-2 victory Monday in the annual Patriots Day game.
The Rays won their seventh in a row, all on the road, and matched the team record for the longest winning streak away from Tropicana Field in one season. Tampa Bay (10-3) completed its first sweep at Fenway Park in a series of three or more games.
"We've got 5½ more months of baseball to play, so a lot can happen in between that time. We just got to keep doing the things we're doing, keep our head straight, do a lot of little things right and I think the rest will take care of itself," Upton said.
Playing on the morning of the Boston Marathon, the Red Sox lost their sixth straight at home, their longest losing streak at Fenway since a 12-game skid in 1994. Boston (4-9) finished 0 for 30 with runners in scoring position during the series, with Jeremy Hermida's two-run homer the only runs in the finale.
"It's kind of weird," Red Sox catcher Victor Martinez said. "Nothing is going our way. Every team we play, it keeps falling their way."
This season's version of the Red Sox was supposed to rely on pitching and defense. They failed badly over the weekend.
"We caught the Red Sox at a right time for us," Rays manager Joe Maddon said. "They're going to be fine. They're going to get hot. They're going to do all those things. We were playing well right now."
Jeff Niemann (1-0) pitched seven sharp innings, giving up two runs and five hits. He held the Red Sox to three hits until Bill Hall singled off the wall and Hermida followed with his homer into the right-field seats with two outs in the seventh.
Lackey (1-1) allowed eight runs and nine hits in only 3 1/3 innings. He didn't get much help from the Boston defense, either, with all three outfielders -- Hermida, Hall and J.D. Drew -- misplaying a ball into an extra base or making an error early in the game.
"It was an opportunity to do that," Lackey said of a chance to end the slide. "It obviously wasn't good."
There were loud boos when Hall watched a ball carom off the center-field wall and away from him, allowing Jason Bartlett to take third. The play was originally ruled a double and an error, but changed later to a triple.
The boos didn't stop when Drew grounded out to end the game.
"We're going through a really tough time," manager Terry Francona said.
Carl Crawford was successful stealing for the 31st straight time against the Red Sox, swiping second in the third inning.
Bartlett opened the game with a double, snapping an 0-for-14 stretch, advanced on Crawford's sacrifice and scored on Ben Zobrist's grounder.
Evan Longoria had a two-run double in the third and Upton hit his homer into the Red Sox bullpen, just past the outstretched glove of Hall, to make it 6-0. It was Upton's fourth homer in five games.
Bartlett added an RBI triple, chasing Lackey and making it 7-0 in the fourth. He scored on Crawford's sacrifice fly.
The Rays have won eight straight road games dating to last season. ... Red Sox CF Mike Cameron was a late scratch because he had similar symptoms to last week when he missed two games to pass a kidney stone. Francona said after the game he was still going through tests. "He had a CT scan, which we think ruled out more (kidney) stones," Francona said.