Guardians vs. Cardinals odds, line, prediction: 2026 MLB picks for Wednesday afternoon from proven model

The Cleveland Guardians and St. Louis Cardinals meet in the third and deciding game of their interleague series on Wednesday afternoon. St. Louis defeated Cleveland 6-5 in 10 innings on Tuesday night. The Guardians (10-8), who have lost three of five, are 6-6 on the road this season. The Cardinals (9-8), who snapped a three-game losing streak, are 6-5 on their home field in 2026.

First pitch from Busch Stadium in St. Louis is set for 1:15 p.m. ET. The Guardians lead the all-time series 24-19, including a 14-10 edge in games played at Busch Stadium. St. Louis is a -114 favorite on the money line (risk $114 to win $100) in the latest Guardians vs. Cardinals odds, while the over/under, is 8.5. 

Before making any Guardians vs. Cardinals 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. It was a profitable 35-29 on top-rated MLB money-line picks last season. 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 Guardians vs. Cardinals 10,000 times and the results are in. The model is going Under on the total, and is also says one side of the money line has ALL the value!

Who wins Guardians vs. Cardinals, and which side of the money line has ALL the value? ... Join SportsLine right now to find out which side of the Guardians vs. Cardinals money line you should be all over, all from the model on a 35-29 roll on top-rated MLB money-line picks!