The slugger hit a tying solo homer with two out in the seventh inning and the Red Sox rallied to beat the Blue Jays 5-1 on Tuesday night.
Saltalamacchia's line drive to left off reliever Jason Frasor just cleared the Green Monster for his 14th homer, tying it at 1. The Red Sox then loaded the bases on a double, a hit batter and a walk before Dustin Pedroia drove in two with a single up the middle.
Saltalamacchia is already closing in on his career high of 16 homers, set two years ago when he shared catching duties with former captain Jason Varitek.
"He's playing a confident brand of baseball because he believes in himself and he's a talented player," manager Bobby Valentine said. "Some things that might have haunted his past just seem to be gone and he's just playing the game of baseball. Looks good doing it."
Adrian Gonzalez and Will Middlebrooks each drove in a run in the eighth and Boston's bullpen completed a solid start by Daisuke Matsuzaka, helping the Red Sox win for the eighth time in 10 games.
"I feel like any given night, it's someone different," said Mike Aviles, who drew a rare walk to load the bases in the seventh for Pedroia.
"Every night you never know who's going to be the hero and that makes the game intriguing for us."
The rally spoiled a strong performance by Aaron Laffey in his first start in nearly two years. Laffey stepped in for Toronto's depleted rotation and pitched six crisp innings, allowing three hits with two walks. Laffey retired 12 straight batters after Aviles' leadoff single in the first.
"Aaron Laffey pitched a heck of a six innings for us," manager John Farrell said. "He gave us six outstanding innings — shutout innings. We were up 1-0."
But that isn't enough at Fenway Park, where the Red Sox had been struggling earlier but improved to 6-2 on a nine-game homestand that wraps up Wednesday afternoon against the Blue Jays.
Andrew Miller (2-0) recorded an out in the seventh to pick up the win. Vicente Padilla pitched a perfect eighth, striking out two and setting up Alfredo Aceves for a 1-2-3 ninth.
After Saltalamacchia went deep, pinch-hitter Ryan Kalish doubled to right against Luis Perez (2-2). David Pauley came out of the bullpen and hit Daniel Nava with a pitch. Pauley then walked Aviles and Pedroia's hit made it 3-1.
"It seems like it's been so long since he's been in that opportunity late in the game where he could win the game," Valentine said. "It presented itself and he drove the runs in. That really gives us strength."
Matsuzaka went 5 2-3 innings, allowing five hits. He struck out five and walked one.
Brett Lawrie led off the game with a double to centre and scored on a two-out single by Edwin Encarnacion, putting Toronto ahead 1-0.
Pedroia walked with one out in the sixth and tried to scamper home on David Ortiz's double off the Green Monster, but Rajai Davis recovered after misplaying the hop and threw a straight shot to catcher Jeff Mathis in time for the tag.
NOTES: The series is tied 1-1 and concludes with an afternoon game Wednesday. Boston's Jon Lester (4-5) is scheduled to face Ricky Romero (8-1). ... The Red Sox announced RHP Clay Buchholz experienced erosion of his esophagus, and the condition caused internal bleeding. The team says he is doing well and is expected to make a complete recovery. ... Laffey's previous start was July 19, 2010. ... Davis led off the second with a single, but Matsuzaka picked him off first.