"We're obviously very much aware that he's had a tremendous season," Trumbo said. "Whether it be at this park or another one, we still have a job to do."
Trumbo blasted a first-pitch slider from Porcello an estimated 448 feet for a homer that easily cleared the Green Monster in left field to lead off the second.
It was his major league-leading 42nd homer of the year and his 100th RBI of 2016, tying a career high set during his 34-homer season with the Los Angeles Angels in 2013.
Baltimore (80-65) moved within a game of first-place Boston (81-64) in the American League East after the Toronto Blue Jays -- who began the day tied for second with the Orioles -- were blown out by the Tampa Bay Rays earlier in the day.
"To think that you could make one run stand up in this ballpark that's got an offensive team that they are is a real tribute to how well Kevin (Gausman) and Zach (Britton) pitched," Baltimore manager Buck Showalter said.
The Red Sox have lost back-to-back games after clocking the O's 12-2 in the series opener on Monday.
"This is going to be a hard-fought division right to the final game of the season," Boston manager John Farrell said. "We fully embrace it."
Gausman (8-10) outdueled Porcello, the majors' first 20-game winner, tossing eight scoreless innings while allowing four hits and one walk and striking out six.
Britton shut down the Red Sox in the ninth to convert his 43rd straight save opportunity to start the year, a major league record for a left-handed pitcher.
Porcello (20-4) suffered his first loss at Fenway this season after going 13-0 in his first 14 starts at the ballpark. He was charged with one run and four hits and fanned six.
Porcello and Dave Ferriss are the only Red Sox pitchers to open a season 13-0 at home. Ferriss accomplished the feat in 1946. No Red Sox pitcher has ever gone 14-0 at home to begin a season.
"We lost and it's a big game," Porcello said. "There's no satisfaction in that."
Boston failed to advance a runner past first base through the first six innings against Gausman, but Chris Young's two-out single to left-center field put runners on the corners with two outs in the seventh.
Gausman got out of the jam, however, striking out Sandy Leon with a splitter.
"I felt like I had him sped up, so I decided to go with the split-finger," Gausman said, "and it was probably one of the best ones I threw all night."
Porcello gave fans a scare two batters after Trumbo's blast as J.J. Hardy's line drive deflected off his left calf. Porcello immediately started limping but stayed in the game after being examined.
"(Hardy) put a good swing on it," Porcello said. "I couldn't get my glove down in time.
"It got me in a good spot. If it got me in the shin it might have been a little bit tougher."
Gausman held the Red Sox without a hit for 3 2/3 innings before Betts hit a line-drive single to right.
NOTES: Baltimore OF Steve Pearce (right forearm) was examined by New York Mets orthopedist David Altchek on Wednesday in New York and received a platelet-rich plasma injection. "We'll let it run its course and see if he's going to be available to us at some point," manager Buck Showalter said. ... Former Red Sox GM Ben Cherington was hired as the vice president of baseball operations for the Toronto Blue Jays. "He's going to make a great contribution, no doubt," said Boston manager John Farrell, whom Cherington hired in 2013. ... Major League Baseball released its 2017 schedule. Baltimore hosts Toronto in its season opener, and Boston opens at home against the Pittsburgh Pirates, both on April 3. ... Orioles RHP Yovani Gallardo (5-7, 5.44 ERA) opposes Rays LHP Blake Snell (5-8, 3.62) on Thursday in Baltimore. Red Sox LHP Eduardo Rodriguez (2-7, 4.70) counters Yankees RHP Masahiro Tanaka (13-4, 3.04) on Thursday at Fenway.