BALTIMORE—This will be remembered as the series in which the Orioles made the strategic mistake of continuing to pitch to a red-hot Randal Grichuk, compounding their own mistakes on the field.

Grichuk homered twice on Wednesday, including a two-run shot in the sixth that turned a 2-1 Orioles lead into a 3-2 deficit on the way to a 5-2 loss, their fourth in a row. Grichuk hit four home runs in three games.

Grichuk gave Toronto a 1-0 lead with his fifth homer of the season in the second against Orioles starter Tommy Milone. It was his two-run homer off Milone in the sixth that changed the game. Milone left a pitch out over the plate, and Grichuk hit his 16th homer in 33 games against the Orioles.

“We’re having a tough time keeping the ball in the ballpark on him,” manager Brandon Hyde said. “He’s taking some really good at-bats on us, made some decent pitches.”

The Orioles had an opportunity in the first when Chance Sisco, who became their first catcher to lead off since Floyd Rayford on June 26, 1985, walked against Tanner Roark. Anthony Santander extended his hitting streak to 14 games with a double, but Sisco was thrown out at the plate on Renato Nuñez’s bouncer to third. Rio Ruiz struck out and Hanser Alberto grounded to second.

“We made a couple of mistakes there,” Hyde said. “One is [Sisco] on third base needs to stay. You need to know yourself, too. If it’s [Andrew Velázquez, it’s a little bit different. If it’s an average or below-average runner at the corner, you’ve got to be sure.

“Second thing is that if the runner in front of you goes on that, you need to advance to third base, and we didn’t do that, either. Two mistakes in one in that first inning.”

It came on the heels of Dwight Smith Jr.’s base-running blunder in the 10th inning Tuesday night when he ran through a stop sign by his third base coach and was caught in a rundown as the Orioles lost, 8-7.

In the second inning on Wednesday, Smith and Pat Valaika singled, but Chris Davis was called out on strikes, Cedric Mullins popped to second and Sisco flied to center.

“Today, for me, wasn’t one of our better games,” Hyde said. “Tommy Milone pitched very, very well. He really gave us a chance to win. Just a couple of balls that Grichuk hit that hurt.

“We shot ourselves in the foot early on by making some mistakes [on] the bases, poor approach with runners on the bases in scoring position that could have made it a lot easier on Tommy, but didn’t.”

Alberto doubled to begin the fourth. Smith singled to right, but Teoscar Hernandez overran the ball for a two-base error, allowing Alberto to score. Valaika’s single scored Smith. Mullins singled to left, and alertly took second when leftfielder Anthony Alford threw to third. Valaika was thrown out at the plate to end the inning when Sisco flied to right.

Ruiz and Alberto had two-out singles in the fifth and advanced to third on Reese McGuire’s passed ball, but Smith popped to center to end the inning.

Grichuk’s second home run of the game gave Toronto the lead for good in the sixth.

“He was on some kind of fire against us,” Milone said. “He’s been hitting well, anyways, but I think the power numbers had just shot up at the wrong time for us to face him. He’s just hot, and he hit a couple of mistakes I left out across the plate. When someone’s hot like that, and they’re hitting a bunch of homers, that’s what’s going to happen. That’s what he did.”

Milone allowed three runs on seven hits in six innings, striking out seven without walking a batter.

Roark allowed two runs, one of them unearned, in five innings but was helped when the Orioles left seven and were 2-for-10 with runners in scoring position.

“When we were winning, we were stringing like five, six, seven at-bats together,” Valaika said. “Lately, it’s been a little hit or miss on that.

“I think anytime you get those opportunities, you’ve got to cash in. They’ve got a good bullpen, and when you’ve got those chances, you’ve got to make the most of them.”

Against Toronto’s relievers, the Orioles had just one more runner in scoring position and left three more on base.

“We didn’t have very many good approaches with runners in scoring position today, which we have had,” Hyde said. “A lot of times we got ourselves out, early swings, things that we have not been doing.”

Brandon Drury’s sacrifice fly to center against Thomas Eshelman in the eighth scored Travis Shaw to give Toronto a 4-2 lead.

In the ninth, Smith overran Cavan Biggio’s pop fly in left for a double. Biggio scored on Lourdes Gurriel’s single against Paul Fry.

After Roark left, Ryan Borucki, Tom Hatch and Rafael Dolis shut down the Orioles. In the ninth, Mullins, who recently has been a bright spot, bunted for a base hit and Santander, the biggest bright spot of late, walked with two outs.

Dolis struck out Davis, who fanned three times for the first out, Sisco for the second and Renato Nuñez to end the game. The Orioles are 12-12.

Evaluating prospects: With such a 60-game season, the Orioles might not have time to evaluate prospects such as first baseman/outfielder Ryan Mountcastle or pitchers Keegan Akin and Dean Kremer if they’re summoned from the alternate site at Bowie,

“I’m not sure, to be honest with you,” Hyde said. “In a normal season, guys come up in September and have really good Septembers and struggle the next year and vice versa. If and when those guys come back and come up, we’re going to give them a look and continue to evaluate them in spring training next year, But, can I make a decision on somebody in a month, that’s pretty unfair.”

Coming up: The Orioles play the Boston Red Sox four times at Camden Yards, beginning Thursday night. Asher Wojciechowski, John Means, Alex Cobb and Wade LeBlanc are scheduled to pitch for the Orioles. Boston will start Nathan Eovaldi on Thursday, Martin Perez on Saturday and Zach Godley on Sunday. Boston hasn’t decided on its Friday night pitcher.