Blue Jays vs. Orioles Prediction, MLB Picks for Monday, September 21

The Toronto Blue Jays (77-79) and Baltimore Orioles (75-81) will open a three-game series at 6:35 p.m. ET on Monday, September 21. This is the second-to-last series of the regular season for both teams, and while the Blue Jays and Orioles are technically still in the race for the final AL Wild Card spot, their chances are slim at best.

Neither team comes into this matchup with a ton of momentum. Toronto is 9-9 this month and just lost two of three against the Texas Rangers. Meanwhile, Baltimore has really struggled down the stretch, going 6-12 in September and most recently getting swept by the Milwaukee Brewers.

Which team will get a much- needed win on Monday? 

Below, we'll break down our Blue Jays vs. Orioles prediction and picks for Monday’s MLB matchup, including the run line, over/under, and key player picks for PrizePicks.

Make your Blue Jays vs. Orioles picks and predictions on PrizePicks now.

{{mlb_offer_banner="/style-system/ui-components-playbook"}}

Blue Jays vs. Orioles Prediction, Winner Payout, Over/Under – Monday, September 21

Monday’s pitching clash will feature Blue Jays SP Trey Yesavage going up against Orioles SP Shane Baz.

Yesavage is returning from knee surgery and last made a start for Toronto in early August. He’s only expected to go roughly 45-50 pitches tonight.

The right-hander has been solid across 18 starts when healthy, though his underlying numbers are a mixed bag. His 3.65 ERA is backed by a 3.40 xERA (78th percentile), 34.0% hard-hit rate (82nd percentile), and 6.1% barrel rate (75th percentile), per Baseball Savant.

On the other hand, his 23.6% strikeout rate is only slightly above average (59th percentile), and his 11.9% walk rate (12th percentile) is an issue. 

Further, Yesavage has benefited from a .215 BABIP and 8.3% HR/FB rate that might’ve regressed over a fully healthy campaign, and his 4.56 SIERA also paints a less flattering picture. 

Particularly coming off a lengthy rehab assignment, it’s difficult to predict how he’ll perform tonight. Additionally, with Yesavage on a pitch count, the Blue Jays will effectively be playing their second straight bullpen game, potentially limiting their relief options. 

Baz has been a workhorse for the Orioles, pitching 173 innings over 30 starts. Although he was removed from his last start after getting hit by a line drive, he avoided any serious injury and figures to have a normal workload on Monday.

The righty has been roughly a league-average starter, logging a 4.11 ERA with similar marks in both xERA (4.21) and xFIP (4.27). While he has a respectable 8.1% walk rate (56th percentile) and 6.9% barrel rate (60th percentile), his 20.5% strikeout rate (36th percentile) and 42.0% hard-hit rate (20th percentile) aren’t anything to write home about.

In all, due to Baz coming in with fewer question marks, Baltimore could have a slight edge on the mound.

The Orioles have been the superior team at the plate in 2026, averaging 4.44 runs per game (15th in MLB) compared to 4.03 for the Blue Jays (29th). Per FanGraphs, Baltimore comes in with a 101 wRC+ (13th), while Toronto is at just a 95 wRC+ (24th).

That being said, the Orioles’ bats have gone quiet this month, producing the second-worst wOBA (.292) and second-worst K-rate (28.2%). That’s in contrast to the Blue Jays posting a solid .324 wOBA and league-best 17.6% strikeout rate over that same span.          

Blue Jays vs. Orioles Winner Payout, Over/Under – Monday, September 21

The Orioles enter Monday’s game as a home favorite against the Blue Jays, returning a 1.85x payout if they win outright, via PrizePicks.

Here are the full payouts for the Blue Jays vs. Orioles game on PrizePicks.

Make your Blue Jays vs. Orioles prediction on the winner or over/under on PrizePicks.

Team Picks data is live at the time of writing and is subject to change.

Blue Jays vs. Orioles Prediction on Over/Under – 9/21/26

Here are the key game stats and trends behind our Blue Jays vs. Orioles prediction on the over/under for Monday, September 21.

Lock in your Blue Jays vs. Orioles prediction on PrizePicks now.

• Yesavage is expected to pitch only about 3 innings tonight. Seven members of the Blue Jays’ bullpen pitched on Sunday, and four have pitched two of the last three days.
• Despite the Orioles’ overall struggles at the plate this month, they’ve put up a 101 wRC+ over the last two weeks.
• Most of Toronto’s top hitters bat right-handed. Baz has a solid 3.63 xERA in same-handed matchups this year.
• Over the last 30 days, Baltimore’s relievers have produced the league’s third-best xERA (3.28).
• This season, Toronto’s bats rank last in xwOBA (.297), second to last in hard-hit rate (34.1%), and third to last in barrel rate (5.8%).

Blue Jays vs. Orioles Picks, Player Stats for PrizePicks: 9/21/26

Here are the top Blue Jays vs. Orioles picks to target on Monday, September 21. Today’s MLB picks for PrizePicks include Kazuma Okamoto and Coby Mayo.

Blue Jays 3B Kazuma Okamoto vs. Orioles: 5 Fantasy Score

• Okamoto boasts a 13.3% barrel rate (89th percentile) and .448 xSLG (78th percentile). That’s helped him to a .224 ISO with 33 home runs.
• He’s been red-hot this month, posting a .397 wOBA and .286 ISO.
• Okamoto has logged at least a hit in 13 of 17 games in September.
• Although Baz has been slightly better against right-handed batters, he’s logged a modest 19.4% strikeout rate in the split. That's particularly notable for Okamoto, who sometimes struggles with strikeouts (28.9% K-rate).

Add Kazuma Okamoto + Blue Jays to cover the spread to your PrizePicks lineup now.

{{mlb_offer_banner="/style-system/ui-components-playbook"}}

Orioles 3B Coby Mayo vs. Blue Jays: 5 Fantasy Score

• Mayo is in the 85th percentile or better in xSLG (.482), barrel rate (13.6%), and hard-hit rate (48.1%).
• The slugger has put up a massive 155 wRC+ since the All-Star break, logging a .390 xwOBA and 16.7% barrel rate over this span. Half of his 24 homers have come since the break, too.
• Mayo has at least a hit in eight of his last 10 games. He's tallied at least 1 run and/or RBI in five of those 10 games.
• Due to his strong play of late, he's now consistently batting third or fourth in the lineup.

Add Coby Mayo + Orioles to win to your PrizePicks lineup now.

Make Blue Jays vs. Orioles Picks on PrizePicks

The Toronto Blue Jays and Baltimore Orioles will try to keep their dwindling playoff hopes alive on Monday. Which AL East team gets the win?

Don’t wait until the first pitch — make your Blue Jays vs. Orioles picks on PrizePicks now and earn real money if you’re right.

Pick players, predict More or Less on their stats, and cash in if you’re right. With Team Picks, you can make predictions on game winners, spreads, and over/unders, now available in 36 states.

Stay locked in on Playbook for daily MLB predictions, picks, and news all the way through the 2026 MLB season.