Upton and Longoria homered off a suddenly shaky Jon Lester, and the power-packed Rays cleared the Green Monster four times to beat the Boston Red Sox 9-1 Monday for a 2-1 lead in the AL championship series.
Rocco Baldelli and Carlos Pena also sent shots over Fenway Park's famous left-field wall as Tampa Bay tied the ALCS home run record. Behind Matt Garza's pitching, the Rays put the defending World Series champions in a postseason hole for the first time since they overcame a 3-1 deficit against Cleveland last year to win the pennant.
"Three-run homers are nice to get. We were very fortunate," Rays manager Joe Maddon said.
The Rays also hit hard on the basepaths. Carl Crawford bowled over Boston catcher Jason Varitek on a play at the plate - there was no immediate reprisal in a matchup between teams that have tangled in the past.
Garza, the only Tampa Bay pitcher to lose in the first-round series against the Chicago White Sox, made an early 5-0 lead stand up. He held the Red Sox scoreless through six innings before they scored in the seventh.
Boston knuckleballer Tim Wakefield faces Andy Sonnanstine in Game 4 of the best-of-seven series on Tuesday night.
Upton, whose shallow sacrifice fly in the 11th inning won Game 2, hit a three-run homer in the third that sailed completely out of the park. It was his fifth home run of the playoffs - he hit only nine during the regular season.
"He did the same thing to the White Sox," Boston manager Terry Francona said. "We didn't locate, and he hit it a long way. Plays center field, steals bases, and he has a chance to get better, which is kind of scary."
Longoria added a solo shot later in the third. Baldelli had a three-run drive in the eighth and Pena hit a solo homer in the ninth.
After Garza left, J.P. Howell escaped a jam and pitched two scoreless innings. Edwin Jackson closed out the victory.
Lester, who hadn't allowed an earned run in four previous postseason outings - including last year's World Series clincher against Colorado - gave up four earned runs on eight hits in 5 2-3 innings. He gave up an unearned run on Varitek's passed ball in the second, then caused his own problems in the third.
Jason Bartlett singled and Akinori Iwamura doubled off the Monster before Upton hit a towering shot that cleared the wall and the Monster Seats atop it - his fifth homer of the playoffs. One out later, Longoria hit his fourth home run of the postseason, tying a rookie record set by Miguel Cabrera in 2003.
A lifetime Ray, Baldelli had never appeared in the postseason before. Pena is well-traveled - this is his fifth team, including the Red Sox - but he somehow managed to avoid appearing in a playoff game until arriving in Tampa Bay.
The four homers tied an ALCS record achieved nine times previously, most recently when the Red Sox hit four on Saturday.
"This kind of stuff doesn't happen very often," Baldelli said.
Upton hit three homers against Chicago in the first round and one against Boston on Saturday. Longoria also homered in Game 2, when the upstart Rays evened the series. Notes: Lester needed just four pitches to get through the first inning, then he walked Longoria to lead off the second. After not allowing a leadoff runner in his previous two playoff starts, he let the leadoff man on in three consecutive innings. ... Boston SS Alex Cora and RF Baldelli started Monday for the first time in the AL championship series. ... Upton has hit safely in six consecutive playoff games. ... RHP Paul Byrd made his first relief appearance since the 2004 playoffs, when he was with Atlanta.