Caleb Wilfinger
Our long national nightmare is finally over. After an eventful offseason that featured plenty of moves that shook up the sport, the MLB regular season is back with a jam-packed 14-game slate on Opening Day. With plenty of baseball action to sink our teeth into, I’ve scoured through the odds board and targeted a pair of MLB best bets on Thursday’s loaded slate.
But before we dive in, don’t forget to check out our MLB picks for every game Opening Day. You can also check out our 2025 MLB futures guide, which features win total futures, best bets on the MVP, Cy Young and Rookie of the Year, division winner selections and World Series predictions from our team of experts. Let’s get into my MLB best bets for Opening Day.
MLB best bets: Chicago Cubs First 5 innings ML over Arizona Diamondbacks (+110)
Odds available at bet365 at time of publishing.
For my first MLB best bet of Opening Day, I’m taking the Cubs in the first 5 innings over the Diamondbacks. Arizona is a team that I’ve invested in from a season-long futures perspective, but the Diamondbacks don’t have a very advantageous matchup in this contest against Chicago starting pitcher Justin Steele. The 2025 campaign got off to a rocky start for the southpaw in Tokyo against the Dodgers, but we can forgive that brief setback considering that he has been dominant against this Arizona lineup historically. In fact, he has 25 strikeouts and an ERA of 1.00 over his last 18 innings pitched against the Diamondbacks.
Not only does Chicago have an edge with Steele on the mound, but the Cubs’ lefty-heavy top half of the lineup is one that profiles well against Diamondbacks starter Zac Gallen, especially since they were top 10 in hard-hit rate against right-handed pitching a season ago (Baseball Savant). The addition of Kyle Tucker certainly will help in this regard, and it’s worth noting that Gallen might be on a bit of a pitch count considering that it’s his first outing of the season. Throw in the fact that Chicago will surely be playing with a heightened sense of urgency following the disappointing 0-2 start, and I like the Cubs to start fast and hold the lead after the first 5 innings in Arizona.
Don’t miss our MLB Opening Day parlay at +1019 odds to celebrate the return of baseball!
MLB best bets: Pittsburgh Pirates First 5 innings run line -0.5 over Miami Marlins (+100)
Odds available at BetRivers Sportsbook at time of publishing.
For my second MLB best bet of the Opening Day slate, let’s take the Pirates to lead after the first 5 innings against the Marlins. I was not impressed at all with the Marlins’ offseason (or lack thereof), and it’s not out of the realm of possibility that this ends up being the worst team in the majors this season if a few things break the wrong way. The lone bright spot for Miami is that Sandy Alcantara is back as the ace of this pitching staff, but he’ll certainly be on a pitch count in his first official start coming off Tommy John surgery. In fact, Alcantara didn’t exceed 57 pitches in any start in spring training, so I wouldn’t expect him to go past 4 innings in this game, unless he’s having an extremely efficient outing.
On the other side, the Pirates will counter with Cy Young favorite Paul Skenes, who will certainly have an advantage in this game against a Marlins lineup that might be historically bad this season. Skenes is coming off a season in which he finished with a 1.96 ERA (xERA 2.53), a strikeout rate in the top 3% of all qualified pitchers and an opponent-expected batting average of .193 as a rookie. Look for the dominant right-hander to pick up right where he left off a season ago, and I’d be surprised if Miami tallied more than 1 run against Skenes here. Ultimately, I want nothing to do with the bullpens in this game, so I’ll take Pittsburgh to lead after 5 innings.
Read our full Pirates vs Marlins prediction
