Orioles vs. Guardians odds, line, start time, picks, best bets for Tuesday, July 22, matchup from proven model

The Baltimore Orioles meet the Cleveland Guardians in the second of a four-game series on Tuesday night. Cleveland earned a 10-5 win over Baltimore on Monday. The Orioles (44-55), who have lost five of six, are 22-30 on the road this season. The Guardians (49-50), who are second in the American League Central, have won eight of their past 10 games.

First pitch from Progressive Field in Cleveland is set for 6:40 p.m. ET. The Orioles have won four of the last six meetings with the Guardians, including two of three. Cleveland is a -160 favorite on the money line (risk $160 to win $100) in the latest Orioles vs. Guardians odds from DraftKings Sportsbook, while the total number of runs Vegas thinks will be scored, or the over/under, is 8 in the latest MLB odds.  

Before you make any Orioles vs. Guardians 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 entered Week 17 of the 2025 MLB season 46-43 on top-rated MLB picks. It has excelled making home run prop picks this season, returning more than 40 units of profit. Anybody following could have seen strong returns!

The model has simulated Orioles vs. Guardians 10,000 times and the results are in. We can tell you the model is going Over on the run total, and it also says one side of the money line has all the value!

Who wins Orioles vs. Guardians, and which side of the money line has all the value? ... Join SportsLine right now to find out which side of the money line you should be all over, all from the model on a 46-43 roll on top-rated MLB picks!