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MLB betting preview (May 21): Padres vs. Blue Jays predictions
Toronto Blue Jays designated hitter Anthony Santander (25) hits a two-run home run against the San Diego Padres during the fifth inning at Rogers Centre.
Photo credit: Nick Turchiaro-Imagn Images
Greg Warren
May 21, 2025, 12:23 EDT
The Toronto Blue Jays will try to hand the San Diego Padres a fifth straight loss when the two teams continue their series at Rogers Centre on Wednesday night.
Vladimir Guerrero Jr. and Anthony Santander both homered, and Chris Bassitt threw six scoreless innings to lift Toronto to a 3-0 win in the series opener on Tuesday. Toronto’s shaky bullpen also combined to toss three scoreless innings, capped by Jeff Hoffman’s 10th save of the season. The shutout was Toronto’s first of the season.
San Diego has lost four straight games, matching its longest losing streak of the season.
Let’s take a look at the game odds for Wednesday’s clash between the Padres and Blue Jays courtesy of bet365.

Padres vs. Blue Jays odds

Padres moneyline odds
+130
Blue Jays moneyline odds
-155
Runline odds
Blue Jays -1.5 (+135), Padres +1.5 (-160)
Game total
Over 8.5 runs (-120), Under 8.5 (+100)
Date/Time
May 21, 7:07 p.m. ET

About the Padres (27-19 SU, 26-20 ATS, 19-26-1 o/u)

The Padres are experiencing a serious power outage right now, managing just three runs across their last four games while going an awful 0-for-25 with runners in scoring position during that span. They managed just five hits on Tuesday, and only one of those was for extra bases, spoiling a solid outing from starting pitcher Dylan Cease, who threw seven innings of three-run ball while striking out six.
Slugger Manny Machado is mired in an 0-for-15 slump despite slashing an impressive .310/.381/.446 on the season, and Jackson Merrill is slashing just .105/.150/.105 over the last seven days. The Padres are hitting just .213 as a team over the past seven days while scoring just eight total runs.

About the Blue Jays (23-24 SU, 29-18 ATS, 22-24-1 o/u)

It’s been a miserable start to the season for Santander, but he did appear relieved after launching his sixth homer of the season on Tuesday. He’s hitting just .185 with a .592 OPS through 42 games after posting an .814 OPS with 44 homers and 102 RBIs last season for the Baltimore Orioles.
Guerrero Jr. is heating up after a mediocre start to the season, slashing .328/.447/.508 with three homers and seven RBIs this month. He hit .269 in April and .263 in a small March sample size, but he’s historically been a slow starter.
Overall, the Blue Jays have struggled to score runs this season and have plated four or less in six straight games. They’re averaging just 3.8 runs per game this season (23rd in the majors) with a .695 team OPS (19th in MLB).

Probable starting pitchers

San Diego: RHP Randy Vasquez (3-3, 3.45 ERA, 4.67 K/9)
Vasquez has been very good this month, allowing just four earned runs over 17 innings of work while striking out 13. However, his three starts this month have been against inferior opponents: the Los Angeles Angels, Colorado Rockies, and Pittsburgh Pirates. The righty owns a bloated 1.49 WHIP, and his 5.58 xERA suggests he’s been punching above his weight so far this season. He ranks in the second percentile in strikeout rate, and in the third percentile in whiff rate.
Toronto: RHP Kevin Gausman (3-4, 4.59 ERA, 8.12 K/9)
Gausman stunk the last time he took the mound against the Tampa Bay Rays, allowing six runs on 10 hits over 5 2/3 innings. He also coughed up three homers in that contest after not allowing a big fly in his previous four starts. In 170 total at-bats, San Diego’s roster is slashing a combined .288/.305/.447 against the veteran right-hander, with Luis Arraez leading the way with seven hits in nine career at-bats (.778 batting average) against him.

Notable injuries

The Padres are a little thin in the starting pitching department, with both Joe Musgrove (elbow) and Yu Darvish (elbow) on the injured list.
Pitchers Ryan Burr (shoulder), Erik Swanson (forearm), Nick Sandlin (lat), and Max Scherzer (thumb) are all on the injured list for the Blue Jays. Infielder Andres Gimenez (quad) is also on the IL.

Weather

There’s a 90% chance of substantial rain on Wednesday evening in Toronto, so the retractable roof at Rogers Centre will be closed.

Padres vs. Blue Jays betting trends

  • The under is 5-0 in San Diego’s last five games.
  • The Blue Jays are 29-18 on the runline this season (best in the majors).
  • The Padres have hit the team total under in 12 of their last 18 road games.

Padres vs. Blue Jays player prop trends

  • Vasquez has walked two or more batters in seven of his nine starts this year (78%) and is -155 to walk over 1.5 batters. His 13.3% walk rate ranks him in just the eighth percentile in MLB.
  • Guerrero Jr. has exceeded his line of 1.5 hits + runs + RBIs in 16 of his last 20 games and at a 68% rate this season. He’s around -145 to beat that line on Wednesday.
  • Bo Bichette has struck out at least once in six straight games and seven of his last eight. He’s -137 to strike out at least once.
  • Merrill has played under his line of 1.5 hits + runs + RBIs in six straight games and is +115 to fail to hit that mark again.

Padres vs. Blue Jays best bets

  • Guerrero Jr. over 0.5 walks: +115 for one unit (best odds @ Betano). This isn’t the sexiest bet in the world, but Vladdy has drawn at least one walk in seven of his last 10 games, 12 of his last 20, and in 49% of his total games this season while ranking in the 92nd percentile in walk rate (14.6%). He’ll also be facing a starting pitcher with serious control issues in this spot, further increasing the likelihood he’ll be pitched around and given a free pass. We’re getting a very good price here at +115 odds on this player prop.
  • Vasquez over 2.5 earned runs: -117 for one unit (best odds @ Pinnacle). Advanced stats suggest Vasquez has been punching well above his weight statistically to this point in the season, and I think the Blue Jays will get to him early and often in this spot. He’s only allowed over 2.5 earned runs in two of his seven starts, averaging 1.9 allowed per game during that span, so it’s a huge red flag that oddsmakers have set a line with such short odds on the over, indicating they don’t have much faith in him to keep runs off the board on Wednesday.

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