MLB Odds, Picks & Predictions: Wednesday (Yankees vs. Giants)
The 2026 Major League Baseball (MLB) regular season gets underway on Wednesday, as the New York Yankees and San Francisco Giants battle at Oracle Park. The first pitch is scheduled for 8:05 p.m. ET, and the game can be streamed exclusively on Netflix. Let’s build our bankroll with our best MLB picks & predictions for Wednesday, March 25th.
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Wednesday’s Best MLB Picks & Predictions
Odds courtesy of FanDuel Sportsbook | All bets are for 1 unit
New York Yankees (-122) at San Francisco Giants (+104) | O/U 6.5 (-122/+100)
The Yankees and Giants open the season at Oracle Park in San Francisco at 8:05 p.m. ET on Netflix.
The weather forecast calls for temperatures around 65 degrees, with winds blowing out at 16-18 miles per hour (MPH). Oracle Park is considered the windiest ballpark in the Majors, with average winds of 18 MPH. Keep that in mind.
The Yankees finished 94-68 last season, tied with the Toronto Blue Jays for the top spot in the American League East. However, the Jays ended up taking the best record in the American League and the division title because of a head-to-head tiebreaker, going 8-5 against New York. Don’t let anyone tell you that every game does not count.
The Giants ended up winning the same number of games as they lost in 2025, going 81-81. San Francisco ended up 12 games off the pace behind the rival Los Angeles Dodgers, and two games behind the Cincinnati Reds for the final Wild Card spot.
New York turned in a +164 run differential in 2025, the best mark in the American League, and second-best in the Majors behind the Milwaukee Brewers (+172). The Yankees went 44-37 on the road, too. San Francisco managed a 42-39 record at home, while posting a +21 run differential.
The Yankees turn to left-handed pitcher Max Fried (19-5, 2.86 ERA, 1.10 WHIP, 189 strikeouts in 2025) as their Opening Day starter. He was especially effective on the road, going 11-3 with a 3.28 ERA and 101 strikeouts in 104.1 innings in 17 starts.
Fried enters this game with a 4-1 record, 2.68 ERA and 1.07 WHIP with 8.0 K/9 in 50.1 innings across eight starts and nine appearances against the Giants in his career, mostly during his time with the Atlanta Braves.
For the Giants, they’ll roll with righty Logan Webb (15-11, 3.22 ERA, 1.24 WHIP, 224 strikeouts in 2025). He had a pair of meaningful starts for Team USA at the World Baseball Classic, so he isn’t quite in mid-season form, but he might have a bit of a head-start over some of the hitters in the Yankees’ lineup. Of course, Aaron Judge was also on the Team USA roster. Webb is 1-2 with a 5.50 ERA, a 1.28 WHIP and 11.5 K/9 across 18 innings in three career starts versus the Yankees.
These teams met last season at Yankee Stadium from April 11-13, with the Giants winning two of the three games, including a 5-4 win as short underdogs (+105) with Webb on the bump. The over cashed in all three meetings, with a total set at eight runs for each of the outings. The over is 6-0 in the past six meetings in this series.
With the winds blowing out and the over cashing in six straight meetings, the over of 6.5 runs looks awfully tempting in this opener. Let’s also back the Yankees, based on Fried’s numbers and the fact that the Giants were just 17-28 versus lefties in 2025.
MLB Picks: Yankees Moneyline (-122) & Over 6.5 Runs (-122)
Joe Williams is a featured writer at BettingPros. For more from Joe, check out his archive and follow him @winwithjoe