MLB Opening Day 2025 has arrived in earnest, with 26 of the 30 MLB teams beginning their seasons on Thursday. Some of the most intriguing matchups are Rangers vs. Red Sox (-120), Mets vs. Astros (-130) and Marlins vs. Pirates (-155). The last of those three will see NL Cy Young favorite Paul Skenes taking the ball versus 2022 Cy Young winner Sandy Alcantara, who returns to the mound for the first time since undergoing Tommy John Surgery in 2023. The 2025 MLB Opening Day slate concludes with Cubs vs. Diamondbacks at 10:10 p.m. ET, with that contest having the highest total of the day at 8.5, per the MLB odds.
Chicago dropped both games of the Tokyo Series to the Dodgers last week, with the Cubs’ offense scoring just four total runs. Chicago is a +105 underdog on the money line (risk $100 to win $105), per the latest MLB lines at Caesars Sportsbook. SportsLine’s proven model has simulated every Thursday MLB game 10,000 times and revealed exact MLB score predictions for the top games of the day. The model enters the 2025 MLB season on a 32-17 roll on top-rated run-line betting picks (+699) that dates back to 2023.
Padres (+1.5) to cover vs. Braves (-175 at BetMGM)
Score prediction: Braves 3.8, Padres 3.5
The Braves will begin the season without Ronald Acuna Jr. (knee), and while they’ll have reigning Cy Young winner, Chris Sale, on the mound, he hasn’t had the best success versus current Padres hitters. Fernando Tatis Jr., Manny Machado and Xander Bogaerts are a combined 16 for 49 (.327) against Sale, so San Diego should be able to get some runs on the board versus him. Meanwhile, no pitcher has a lower ERA than Padres starter, Michael King (2.79), since the start of 2022. The model has Atlanta narrowly winning but San Diego winning on the run line in nearly 70% of simulations.
Astros to defeat the Mets (-126 at FanDuel)
Score prediction: Astros 5.2, Mets 4.6
While the Mets added Juan Soto, the Astros also had several notable additions, including Christian Walker and Isaac Paredes, both of whom had 30-plus homers as recently as 2023. Houston has its ace on the mound in Framber Valdez, who has a 3.06 ERA over the last three seasons, while the Mets will counter with Clay Holmes, who hasn’t made a start since 2018. Additionally, the Astros have owned this recent series, winning eight of the last 10 games. FanDuel Sportsbook is currently offering the best odds on Houston to win at -126.
Angels to defeat White Sox (-160 at BetMGM)
Score prediction: Angels 5.3, White Sox 4.4
Chicago went an MLB-worst 41-121 last season, with the 121 losses being the most in MLB history. This year, its win total of 53.5 is the lowest for any team in over 35 seasons. The White Sox had both the lowest team batting average and the highest team ERA last season, and while they made offseason improvements, there is still lots of ground to make up. As for the Angels, while Mike Trout has had difficulty staying on the field in recent years, he’s always healthy to start the year and did have the second-highest home run percentage (7.9%) of his career in 2024. Thus, the model has the Angels winning on the money line in almost 60% of simulations.
Reds (+1.5) to cover vs. Giants (-180 at DraftKings)
Score prediction: Giants 4.7, Reds 4.3
Giants’ probable starter, Logan Webb, has allowed just a .225 average to current Reds hitters, however, his counterpart in Cincinnati’s Hunter Greene has seen current Giants batters hit just .133 off him. Greene had a breakout 2024 season, finishing second amongst all NL pitchers in WAR (6.2). The Giants ranked in the bottom five of the NL in both batting average and OPS last season, and then they lost Michael Conforto this season after he was third on San Fran in homers and total bases in 2024. SportsLine’s MLB model has the Giants winning but backs the Reds on the run line as Cincy covers well over 60% of the time.
Mariners to defeat Athletics (-170 at bet365)
Score prediction: Mariners 4.6, Athletics 3.3
The Athletics were one of five MLB teams to average under 4.0 runs per game last season, and the model predicts they’ll even fail to match last year’s 3.97 average. The A’s are projected for just 3.3 runs with Logan Gilbert on the mound for Seattle. The current Athletics roster is just 7 for 78 (.090) against the 2024 All-Star, as Gilbert has more strikeouts (28) than total bases allowed (20) versus the franchise which formerly called Oakland home. The model is all over the Mariners to win on the money line in an A-rated ML pick that hits over 70% of the time. bet365 Sportsbook is currently offering the best price on this bet.
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