The Chicago White Sox (76-73) and the Cleveland Guardians (76-74) open a 3-game AL Central series Monday at Progressive Field in Cleveland, Ohio. First pitch is scheduled for 6:40 p.m. ET. Let's analyze MLB odds around the White Sox vs. Guardians odds and make our expert MLB picks and predictions for the best bets.
Season series: White Sox lead 6-4
The White Sox suffered a 3-1 loss in the interleague series finale in St. Louis Sunday, as Chicago dropped 2 of 3 against the Cardinals. LF Sam Antonacci went 1 for 4 with a triple out of the leadoff spot. The White Sox are 1-5 in the past 6 games, and 4-10 across the past 14 outings. The Under has cashed in 3 of the past 5 games, while going low in 9 of the past 15 outings.
The Guardians took 2 of 3
from the Minnesota Twins on the road, including a 9-2 win as underdogs (+104) as the Over (8) cashed Sunday. CF-LF Steven Kwan went 3 for 4 with a double, home run, walk, 2 runs and 2 RBIs out of the leadoff spot, and Cleveland had 5 hitters with 2 or more hits, while collecting 14 hits overall.
The White Sox are clinging to a half-game lead in the AL Central, while going 33-42 on the road. Chicago is 27-15 inside the AL Central. The Guardians have managed just a 36-39 at home, while they're 25-21 inside the AL Central. Cleveland faces LHP Sean Newcomb in the series opener Monday, and it is 27-23 vs. LHP.
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White Sox at Guardians projected starters
LHP Sean Newcomb vs. RHP Gavin Williams
Newcomb (2-4, 2.77 ERA) makes his sixth start (55th appearance). He has a 1.14 WHIP, 3.2 BB/9, 8.3 K/9 in 84 1/3 innings.
- Last start: No-decision, 1 1/3 IP, 1 ER, 1 H, 1 B, 4 K in 6-5 win at Cardinals Saturday
- 2026 road splits (4 starts, 24 appearances): 0-3, 3.51 ERA (41 IP, 16 ER), 1.12 WHIP, 1 HR, 15 BB, 38 K
- 2026 vs. Guardians (6 relief appearances): 0-1, 1.23 ERA, 2 SV (7 1/3 IP, 1 ER), 5 BB, 8 K
- Career vs. Guardians (8 relief appearances): 0-1, 0.87 ERA (10 1/3 IP, 1 ER), 1.07 WHIP, 11.3 K/9
Williams (13-7, 3.78 ERA) makes his 30th start. He has a 1.09 WHIP, 2.8 BB/9, 12.1 K/9 in 169 innings.
- Last start: No-decision, 6 IP, 2 ER, 4 H, 3 BB, 11 K in 3-2 win in 10 innings vs. Detroit Tigers Sunday
- 2026 home splits (16 starts): 7-3, 3.01 ERA (95 2/3 IP, 32 ER), 1.06 WHIP, 12 HR, 29 BB, 134 K
- 2026 vs. White Sox (3 starts): 0-0, 4.11 ERA (15 1/3 IP, 7 ER), 2 HR, 5 BB, 21 K
- Career vs. White Sox (6 starts): 1-1, 4.91 ERA (29 1/3 IP, 16 ER), 1.40 WHIP, 10.7 K/9
White Sox at Guardians odds
Provided by BetMGM Sportsbook; access USA TODAY Sports Scores and Sports Betting Odds hub for a full list. Lines last updated at 5:38 a.m. ET.
- Moneyline (ML): White Sox +125 (bet $100 to win $125) | Guardians -155 (bet $155 to win $100)
- Run line (RL)/Against the spread (ATS): White Sox +1.5 (-190) | Guardians -1.5 (+154)
- Over/Under (O/U): 7 (O: +105 | U: -125)
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White Sox at Guardians picks and predictions
Prediction
Guardians 4, White Sox 3
Moneyline
The GUARDIANS (-155) are worth a look as moderate favorites in this crucial series opener, as Cleveland looks to flip the division lead in its favor.
Williams is fantastic at home, and he can be trusted to get the job done against Newcomb, who has struggled at times on the road.
Run line/Against the spread
If you can't take Chicago straight up, White Sox +1.5 (-190) is just a little too expensive. My personal limit is -180 for a standalone wager. You can't risk nearly 2 times your potential return, as there is just no value there.
PASS.
Over/Under
OVER 6.5 (-140 at FanDuel Sportsbook) is the lean, but roll with a half-unit play at most.
The Guardians have cashed high in 4 of the past 6 games, while going 3-1 in the past 4 meetings with the White Sox.
For the ChiSox, the Over has a 5-3 mark in the past 8 outings, while 8-5 across the past 13 games vs. AL Central opponents.
Betting odds calculator
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This article originally appeared on Sportsbook Wire: Chicago White Sox at Cleveland Guardians odds, picks and predictions
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