Yankees vs. Guardians odds, line, prediction, start time: 2025 MLB picks, April 21 best bets from proven model

Red-hot teams battle when the New York Yankees take on the Cleveland Guardians in a key American League matchup on Monday night. Cleveland defeated Pittsburgh 5-4, while New York downed Tampa Bay 4-0 on Sunday. The Yankees (14-8), who are first in the AL East, have won six of their past seven games. The Guardians (12-9), who are second in the AL Central, have won three in a row and are 5-1 on their home field in 2025.

First pitch from Progressive Field in Cleveland is set for 6:10 p.m. ET. The Yankees have won six of the last seven meetings against the Guardians. New York is a -130 favorite on the money line (risk $130 to win $100) in the latest Guardians vs. Yankees odds from DraftKings Sportsbook, while the total number of runs Vegas thinks will be scored, or the over/under, is 8.5. Before making any Yankees vs. Guardians picks, be sure to see the MLB predictions and betting advice from SportsLine’s proven computer model.

The SportsLine Projection Model simulates every MLB game 10,000 times. It enters Week 4 of the 2025 MLB season on an 8-3 run on MLB money-line betting picks (+340). Anybody following at sportsbooks and on betting apps could have seen strong returns.

Now, the model has set its sights on Yankees vs. Guardians and just locked in its picks and MLB predictions. You can head to SportsLine now to see the model’s picks. Here are several MLB odds and betting lines for Yankees vs. Guardians:

Yankees vs. Guardians money line: New York -130, Cleveland +110 at DraftKings Sportsbook
Yankees vs. Guardians over/under: 8.5 runs
Yankees vs. Guardians run line: New York -1.5 (+136)
NYY: The under is 5-4-1 in the past 10 Yankees games
CLE: The over is 6-2-2 in the past 10 Guardians games
Yankees vs. Guardians picks: See picks at SportsLine
Yankees vs. Guardians streaming: FuboTV (Try for free)

Why the Yankees can cover

Right-hander Clarke Schmidt (0-0, 4.76 ERA) is expected to get the start for New York. In his first start this season in a 4-3 win over the Kansas City Royals, he pitched 5.2 innings, allowing four hits, three runs — all earned — with two walks and two strikeouts. He started 16 games for the Yankees a year ago, going 5-5 with a 2.85 ERA. In four career starts against the Guardians, Schmidt is 3-1 with a 3.52 ERA.

Right fielder Aaron Judge has been on fire to start the season. In 22 games, he is batting .390 with five doubles, seven homers, 25 RBI and 21 runs scored. In Saturday’s 10-8 loss at Tampa Bay, Judge was 3-for-5 with three RBI. He was 3-for-3 with one double, one homer and one RBI in a 4-3 win over the Kansas City Royals on Wednesday. In 36 career games against Cleveland, Judge is hitting .254 with 11 doubles, 10 homers and 22 RBI. See which team to back at SportsLine.

Why the Guardians can cover

Cleveland will counter with right-hander Gavin Williams (1-1, 4.58 ERA). In four starts this season, he has allowed 16 hits, 10 earned runs and 10 walks, with 18 strikeouts in 19.2 innings. In a 6-1 win over the Chicago White Sox on April 10, he pitched five innings, allowing three hits, one earned run and two walks with seven strikeouts. In one career start against the Yankees, he is 0-1 with a 6.23 ERA.

Left fielder Steven Kwan has hits in nine of the last 10 games, including four in a row. He has four multi-hit games during that span, including a 4-for-5 performance with one homer, four RBI and two runs scored in a win over the White Sox on April 10. In this past weekend’s three-game sweep of the Pirates, Kwan was 5-for-12 with a double, one home run and three RBI. In 18 career games against the Yankees, he has 13 hits and nine walks with four stolen bases. See which team to back at SportsLine.

How to make Yankees vs. Guardians picks

SportsLine’s model is leaning Over on the total, projecting 9.7 combined runs, and it says one side of the money line has all the value. You can head to SportsLine to see the model’s MLB picks.

So who wins Yankees vs. Guardians, and which side has all the value? Visit SportsLine now to see which side you need to jump on, all from the model that has crushed its MLB picks, and find out.