Astros vs. Cubs odds, line, prediction: 2026 MLB picks for Friday, May 22, from proven model

The Chicago Cubs and Houston Astros hope to turn things around after tough starts to the week, when they face off in a Friday matinee to being a three-game interleague series. The Cubs (29-21) just got swept at home by the rival Brewers and have lost eight of 10 to fall out of first place in the rugged NL Central. The Astros (20-31) have scored five runs in their last four games combined, losing three of them to fall further back from the Athletics in the AL West. Houston starts Spencer Arrighetti (5-1, 1.50 ERA) against Chicago's Jameson Taillon (2-3, 4.94). 

First pitch from Wrigley Field in Chicago is set for 2:20 p.m. ET. Chicago is a -141 favorite on the money line (risk $141 to win $100) in the latest Astros vs. Cubs odds, with Houston priced at +120 (risk $100 to win $120). The over/under is 7. 

Before making any Astros vs. Cubs picks, or MLB predictions, you NEED to see what the SportsLine Projection Model has to say.

The SportsLine Projection Model simulates every MLB game 10,000 times and enters Week 9 of the MLB season on a sizzling 12-1 run on all top-rated MLB picks. It also excelled at making home run prop picks in 2025, returning nearly 30 units of profit. Anybody following could have seen strong returns!   

The model has simulated Astros vs. Cubs 10,000 times and the results are in. The model is going Over on the total, and is also says one side of the money line has ALL the value!

Who wins Cubs vs. Astros, and which side of the money line has ALL the value? ... Join SportsLine right now to find out which side of the Astros vs. Cubs money line you should be all over, all from the model that enters Week 9 of the MLB season on a red-hot 12-1 run!