The final weekend of the Major League Baseball regular season is upon us. We are set up for drama right to the very last day, given how tight several division and Wild Card races are.
Read on for my top MLB picks & predictions for Friday, September 26th.
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Friday’s Best MLB Picks & Predictions
(Odds courtesy of DraftKings Sportsbook)
St. Louis Cardinals (+144) at Chicago Cubs (-176) | O/U 9.0 (-101/-121)
The Cubs bounced back from their longest losing streak of the season (five games) with a win on Wednesday against the Mets. I cannot back Chicago's Moneyline odds confidently enough given its recent struggles, but the way its offense performed at home after a seven-game road trip has me looking towards the over as my best bet for this afternoon’s tilt.
Chicago averaged just 3.3 runs per game over a 3-4 seven-game road trip, all of which were against division rivals. But 16 of those 23 runs scored in that span came in a three-game road sweep of the Pirates, and there was enough to like about Chicago's offense in its return home against New York to think it can cash this over by itself.
The Cubs exploded for 22 runs and hit five home runs in the three games, as they went 11-for-25 with runners in scoring position. Now they face a familiar foe in Cardinals righty Miles Mikolas, who has allowed a .323/.348/.539 slash line with 24 extra-base hits in 192 combined at-bats to current Cubs hitters.
All four hitters (Dansby Swanson, Seiya Suzuki, Ian Happ, Nico Hoerner) with 25+ career at-bats against Mikolas have combined for a .311 batting average and 12 RBI, so the Cubs could come close to cashing this over by themselves.
Pick: Over 9.0 Runs (-101)
Baltimore Orioles (+123) at New York Yankees (-150) | O/U 8.5 (-102/-119)
It is crazy to think that the season Trevor Rogers is having has gone under the radar, but that tends to happen when one misses a significant amount of time due to injury while playing on a bad team.
Rogers is 9-2 with a 1.35 ERA and has allowed 16 earned runs in 17 starts. This is his second consecutive start against a Yankees team that he shut out over six innings while holding them to one hit and striking out seven. I am not concerned that the Bronx Bombers are seeing him twice in a short span, as he made consecutive starts against the Texas Rangers earlier in the year and held them to just two earned runs over 13.1 innings.
Pick: Yankees Team Total Under 4.5 Runs (-130)
Pittsburgh Pirates (+134) at Atlanta Braves (-163) | O/U 8.5 (-115/-106)
Ronald Acuna Jr. has 20 home runs in 92 games this year, which would extrapolate to 35 home runs over a full season. He is in midseason form in September with five home runs (all within the last 15 days) and a .900 OPS. He has also belted three home runs this week alone, adding to an eye-popping 1.214 OPS.
Acuna has great career numbers against Pirates righty Mitch Keller, going 7-for-18 with three of the hits being home runs. He should again provide outstanding protection for teammate Matt Olson in the lineup, as those two are the only batters in tonight's lineup with a 1.145 OPS or better in their careers against Keller (minimum 10 at-bats).
DYK: Ronald Acuña Jr. is the only player to debut in the Divisional Era (1969) to average 30+ HR and 30+ SB per 162 games played (min. 800 games played)
The Venezuelan standout is a 5-time All-Star and was named NL MVP in 2023 when he became the first player in MLB history to... pic.twitter.com/GhT3ipTkZe
— MLB (@MLB) September 24, 2025
Pittsburgh is 1-6 in Keller's last seven starts, with the righty allowing at least one home run in six straight. He has followed up a 6.52 ERA in August with a 4.32 ERA through three September starts, which are on pace to be two of his worst three months of the season.
All things considered, these are great odds for one of the sport’s best hitters to go yard.
Pick: Ronald Acuna Jr. to Hit a Home Run (+356)
Mike Spector is a featured writer at BettingPros. For more from Mike, check out his archive and follow him @MikeSpector01