Astros vs. Cubs Prediction, MLB Picks for Friday, May 22

First pitch for the Houston Astros vs. Chicago Cubs game is set for 2:20 p.m. ET on Friday, May 22, with the Cubs entering as home favorites and returning a 1.63x payout on PrizePicks Team Picks if they win. 

Today’s game is the first of three in the only series between these two teams this season. Both sides aim to turn around a mediocre run of games, as the Cubs are 2-8 over their last 10 while the Astros are 4-6.

Below, we'll break down our Astros vs. Cubs prediction and picks for Friday’s MLB game, including the spread, over/under, and key player picks for PrizePicks.

Make your Astros vs. Cubs picks on PrizePicks now.

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

Astros vs. Cubs Prediction, Winner Payout, Over/Under – Friday, May 22

The Astros’ season has been quickly unraveling recently, as they now sit at 20-31, good for fourth place in the American League West. They’ve suffered some injuries, recently adding 2B Jose Altuve to the 10-day IL with a Grade 2 left oblique strain and losing 3B Carlos Correa for the season with a torn tendon in his ankle.

Houston has also been a disaster on the mound with a starting rotation that ranks 26th with a 4.43 xFIP.  

The Cubs have stumbled upon rough times recently, having lost five straight games and 9 of their last 11. This rough stretch has seen their overall record drop to 29-21 and allowed the Milwaukee Brewers to take a 1.5-game lead in the NL Central.

Chicago could still have a promising season ahead of it, as its +28 run differential is fourth-best in the NL. Before this rough stretch, the Cubs were on a 10-game winning streak.

Astros vs. Cubs Winner Payout, Over/Under – Friday, May 22

The Cubs enter Friday’s game as home favorites against the Astros, returning a 1.63x payout if they win outright, via PrizePicks Team Picks.

Here are the full payouts for the Astros vs. Cubs game on PrizePicks.

• Spread: Chicago Cubs -1.5 (2.38x payout)
• Over/Under: 7.5 (1.69x payout on Over)
• Game Winner Payout: Astros 2.12x | Cubs - 1.63x

Play the Astros vs. Cubs spread or over/under on PrizePicks Team Picks to earn real money — available in 35 states!

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

Astros vs. Cubs Prediction on Spread – 5/22/26

Here are the key game stats and trends behind our Astros vs. Cubs prediction on the spread for Friday, May 22.

Lock in your Astros vs. Cubs prediction on PrizePicks now.

• Over the last week, the Astros have a wRC+ of 50. That trails only the Colorado Rockies for the worst in the sport. 
• Cubs SP Jameson Taillon might be due for some positive regression given his unsustainably high 20.8% HR/FB%, which is 8.1% above his career average.
• Meanwhile, Astros SP Spencer Arrighetti may be staring down negative regression soon. He has an xFIP over three runs above his ERA, as well as a BABIP of .231 and a HR/FB% of 2.7%.  
• The Cubs are a notoriously patient team at the plate and match up well against Arrighetti, who can struggle mightily with his command, as seen by his 5.25 BB/9.
• Finally, the Astros' bullpen has been an absolute disaster, ranking dead last in the majors in xFIP at 4.94.

Astros vs. Cubs Picks, Player Stats for PrizePicks: 5/22/26

Here are the top Astros vs. Cubs picks to target on Friday, May 22. Today’s MLB picks for PrizePicks include SPs Spencer Arrighetti and Jameson Taillon.

Astros P Spencer Arrighetti vs. Cubs: 5 Strikeouts

• Arrighetti runs into a difficult matchup against a Cubs team that is striking out just 21.3% of the time this season, the 10th-lowest rate in MLB. They also walk the second-most often at 11.6%.
• His 1.50 ERA sits well below his 4.68 xFIP, suggesting that a short start could be in his future.
• The standout pitcher’s 10.5% swinging strike rate is lower than last season and the lowest of his three-year career.
• In fairness, Arrighetti has shown much better strikeout stuff at home this season, with a 10.18 K/9 in Houston compared to a 6.89 K/9 in away contests.

Add Spencer Arrighetti to your PrizePicks Lineup now.

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

Cubs P Jameson Taillon vs. Astros: 4.5 Strikeouts

• Taillon had a 6.8 K/9 in 2024 and 2025 but has shown better strikeout stuff this year, owning a 7.46 K/9.
• He also has a SwStr% of 10.6%, which is 1.4% higher than last year and his highest mark since 2021.
• Houston has the fourth-highest K-rate over the last week at 26.1%.
• Taillon has had a higher K/9 at home every season since 2022. This year, he holds an 8.87 K/9 at home compared to 6.35 on the road.

Add Jameson Taillon to your PrizePicks Lineup now.

Make Astros vs. Cubs Picks on PrizePicks

Today’s 15-game slate is kick-started by some Friday afternoon baseball in Wrigley. Which team will be able to turn around some rough sledding and pick up the first win of this three-game series?

Don’t wait until lock — make your Astros vs. Cubs 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 35 states.

Stay locked in on Playbook for daily MLB predictions, picks, and news every day all the way through the 2026 MLB World Series.