Orioles vs. Guardians odds, line, prediction, time: 2025 MLB picks, best bets for July 22 by 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 -142 favorite on the money line (risk $142 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 8.5. Before making any Orioles vs. Guardians picks, be sure to see the MLB predictions and betting advice from SportsLine’s proven computer model.

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 at sportsbooks and on betting apps could have seen strong returns.    

Now, the model has set its sights on Orioles vs. Guardians and just locked in its picks and MLB predictions. You can head to SportsLine now to see the model’s picks. Here are several MLB odds and betting lines for Orioles vs. Guardians, which you can get in on with a DraftKings promo code or a FanDuel promo code.

Why the Guardians can win

Left-hander Joey Cantillo (1-0, 4.17 ERA) is expected to make his fourth start of the year and 25th appearance. In 41 innings pitched this season, he has allowed 39 hits, 19 earned runs and 20 walks with 54 strikeouts. In his last appearance, a no-decision on July 13, he pitched 5.1 innings, allowing seven hits, four earned runs and no walks with six strikeouts in a 6-5 win over the Chicago White Sox. In a 1-0 loss to the Chicago Cubs on July 3, he pitched 3.1 innings, allowing two hits and three walks with five strikeouts.

Among Cleveland’s top hitters include Jose Ramirez. In 96 games this season, he is hitting .294 with 18 doubles, two triples, 20 homers, 55 RBI and 29 stolen bases. He has hits in six of the past 10 games, including a 2-for-3 performance in an 8-6 win over the Athletics on Friday. In that game, he doubled, tripled, walked and scored two runs. He drove in three runs with a homer in Monday’s win. See which team to back at SportsLine.

Why the Orioles can win

Right-hander Brandon Young (0-4, 7.52 ERA) is expected to start for Baltimore. In six starts this season, he has logged 26.1 innings, allowing 36 hits, 22 earned runs and 11 walks with 25 strikeouts. In a no-decision against the New York Mets on July 8, he pitched 5.1 innings in a 7-6 loss. He allowed five hits and two earned runs with six strikeouts.

Helping lead the Baltimore offense is shortstop Gunnar Henderson. In 92 games, he is batting .279 with 22 doubles, four triples, 11 homers, 35 RBI and 13 stolen bases. In a 7-3 win over the New York Mets on July 10, he was 3-for-5 with a double. He was 2-for-4 with two doubles in a 6-0 loss to the Miami Marlins on July 12. He has hits in seven of the last nine games. See which team to back at SportsLine. 

How to make Orioles vs. Guardians picks

SportsLine’s model is leaning Over on the total, projecting 8.7 combined runs, and it says one side of the money line has all the value. You can head to SportsLine to see the model’s MLB picks. 

So who wins Orioles vs. Guardians, and which side of the money line has all the value? Visit SportsLine now to see which side you need to jump on, all from the model that has crushed its MLB picks, and find out.