We have a loaded MLB slate on Wednesday, giving us plenty of betting opportunities in both the afternoon and evening.
Let's dig right into today's MLB best bets, which include props, picks and predictions for Guardians vs. Twins, Mets vs. Red Sox and Padres vs. Blue Jays.
Find all of our Wednesday MLB best bets — and a parlay of all our picks — below.
MLB Best Bets, Props, Picks — Wednesday, May 21
| Game | Time (ET) | Pick |
|---|---|---|
  | 6:45 p.m. | |
  | 7:07 p.m. | |
  | 3 p.m. | |
Specific betting recommendations come from the sportsbook offering preferred odds as of writing. Always shop for the best price using our MLB Odds page, which automatically surfaces the best lines for every game. | ||
Guardians vs Twins Game 2 Best Bet: Utilize This System
By Bet Labs
The second game of today's Guardians-Twins doubleheader has our 'PRO: Contrarian Unders for Winning Teams' lighting up.
This system activates during the regular season when the over/under percentage is between 0 and 35% (meaning the majority of the money is being placed on the over) and both teams feature winning records.
At the time of writing, only 35% of the money is currently on the under for this game featuring two pitchers in Gavin Williams (Guardians) and Chris Paddack (Twins).
Pick: Under 7.5
Mets vs Red Sox Best Bet: Trust the 'Dog
By Bet Labs
Road underdogs playing interleague games have historically been undervalued by oddsmakers. Since 2016, despite winning only 43.3% of these games, these teams have generated a consistent positive ROI of 4.6%.
This trend has proven reliable across five consecutive seasons, indicating market inefficiencies in how these specific matchups are priced — likely due to lack of familiarity between leagues and public overconfidence in home and favorite teams.
In interleague play, road underdogs have shown themselves to be profitable on the moneyline recently. They have only a 43.3% win percentage, but those teams have turned a 4.6% ROI for bettors since 2016 and have been profitable in five consecutive seasons.
This game between the Mets and Red Sox lights up this system as New York heads to Fenway Park for a night game on Wednesday on MLB Network.
Pick: Mets ML +124
Grant Neiffer's Padres vs Blue Jays Best Bet: This Star to Homer?
Manny Machado has gotten off to a rough start to the season, but his underlying power numbers are similar to years past, and this matchup is great.
