Another Toronto squad played to a 2-0 win over the New York Yankees in nearby Tampa, with manager John Gibbons looking on. Bench coach DeMarlo Hale led the Jays (2-1) in their home spring opener before 3,802 at Florida Auto Exchange Stadium on a cloudy 22 C day.
In Tampa, Yankees outfielder Curtis Granderson broke his right forearm when he was hit in the first inning by Toronto starter J.A. Happ. The Yankees expect the slugger to be out for some 10 weeks.
At Dunedin, Santos came in the third inning for his first action since last April, when he was shut down after just six appearances as the Jays closer. He had shoulder surgery in July.
Santos hit 95 m.p.h. twice in retiring the Orioles (2-0) in order in the third, finishing off the inning with a nice stab fielding play on the mound.
"For my first inning and being Feb. 24, I'll take it," said Santos. "It's good. The ball was coming out free and easy."
And he wasn't hurting, as he did last season. Santos threw one slider and five fastballs, all for strikes.
Santos' performance is encouraging to a team still waiting on Casey Janssen, who is also making his way back from shoulder surgery. Janssen, who took over as closer last season in Santos' absence, hopes to be ready by Opening Day but is sticking to a slow and measured program.
Bautista showed he was back from wrist surgery when he homered off Troy Patton in the third, sending the ball into the protective mesh in front of the scoreboard and driving in Jose Reyes for a 3-2 lead.
He had come close in the first, slamming a ball to the warning track in right field.
"It feels good," Bautista said. "I took a couple of big hacks today in good hitters' count. It felt perfect. It feels good to connect (with) the ball after a while (of) not playing."
Santos enjoyed watching Bautista go long.
"We've got a lot of great pieces," he said. "I think if we stay healthy and play the way everybody's played in the past, then I like our chances."
Mark Buehrle started for the Jays, retiring the first four Orioles he faced. Then the bottom fell out and the veteran left-hander exited, after giving up a single, Steve Pearce's homer, single and single to the next four batters in the second, having thrown 35 pitches and 24 strikes.
Pearce split 2012 with the Astros, Orioles and Yankees in addition to Scranton/Wilkes-Barre.
Bobby Korecky came in and cleaned up the mess.
"Obviously the second inning, I didn't locate (the ball) as well," said Buehrle, who seemed unfazed by what was essentially a short practice outing.
"Seems like I never pitch too good in spring training," he added. "My number aren't good."
The 33-year-old Buehrle came over to Toronto in the blockbuster trade with Miami in November. In 2012, the left-hander went 13-13 with a 3.74 earned-run average and 125 strikeouts in 202.1 innings.
It was the 12th straight season Buehrle had posted 10 wins, 30 starts and 200 innings pitched.
Toronto left-hander Aaron Loup followed Santos with a 1-2-3 inning. Jeremy Jeffress had two strikouts in his hitless one inning.
Despite the loss, the Jays pitchers did well with two walks and 10 strikeouts among them. Their Baltimore counterparts had five walks and five strikeouts.
Jair Jurrjens, a native of Curacao who represented the Netherlands at the 2006 World Baseball Classic, pitched the first two innings for the Orioles (2-0). The 27-year-old split last season with the Atlanta Braves and triple-A Gwinnett Braves.
Veteran Mark DeRosa had put the Jays on the board in the second with an RBI single, bringing home J.P. Arencibia from second.
An RBI single by Pearce in the sixth tied it at 3-3 and Baltimore pulled ahead 5-3 in the eighth on a Jason Pridie RBI double and Yamaico Navarro RBI single off Tommy Hottovy, whose cause was not helped by a Ryan Goins error.
Kevin Ahrens closed the gap to 5-4 with a sacrifice fly in the bottom of the eighth.
Toronto came close in the ninth, with Adam Loewen on second and Mike Nickeas on first, but Baltimore right-hander Rob Delaney got Josh Thole for the final out and the save.
Mike Belfiore got the win with one inning of scoreless relief while Hottovy took the loss.
Toronto left 11 on base, compared to eight for Baltimore.