San Diego Padres vs Chicago Cubs Prediction 4/4/25 MLB Picks

The San Diego Padres and the Chicago Cubs meet Friday in MLB action from Wrigley Field. This will be the first installment in a three-game weekend series. Here’s a Cubs vs Padres prediction. We will look at this from a betting perspective and determine the best Cubs vs Padres pick. We will examine: 

The San Diego Padres recent form and player performance

The Chicago Cubs recent form and player performance 

Recent betting trends and streaks involving the San Diego Padres

Recent betting trends and streaks involving the Chicago Cubs

Recent betting trends in games played between the Cubs and Padres

A summary that ties it all together and produces a favorable betting outcome for the Cubs vs Padres game

San Diego Padres Betting Preview

The Padres opened up their year with a four-game series versus the Atlanta Braves. San Diego managed to sweep that one with victories 7-4, 4-3, 1-0 and 5-0. In the Sunday shutout win, the Padres’ Fernando Tatis put up two hits, two runs, two walks and an RBI on a 2-for-3 day. 

San Diego’s second set was against the Cleveland Guardians. The Padres kept their streak going with victories 7-2 Monday and 7-0 in game two. In the Wednesday finale, the Padres posted four runs in the third inning and managed to power out a 5-2 win in the end on the strength of 10 team hits. Luis Arraez (two runs; two hits) and Jackson Merrill (two RBI; two hits) each posted a home run in the victory. Starting pitcher Dylan Cease lasted 6.1 innings with one earned on four hits and one walk alongside seven strikeouts. 

In the Friday starting pitcher slot for the weekend series opener, the Padres are going with Randy Vasquez. In his first start this year Vasquez put up a no-decision with 6.0 clean frames. Over his career Vasquez is 6-9 with a 4.13 ERA in 32 games (26 starts). 

Chicago Cubs Betting Preview

Over on the Cubs’ side, they opened up the 2025 season with a four-game series against the Arizona Diamondbacks (after a couple earlier overseas games versus the Dodgers, that is). Chicago won 10-6 Thursday and 4-3 Saturday but lost the other pair 8-1 and 10-6. In the Sunday loss the Cubs got home runs from Seiya Suzuki (two RBI; two runs), Kyle Tucker (three RBI) and Dansby Swanson (two hits). 

Matched up against the Oakland Athletics this week, the Cubs took victories 18-3 Monday and 7-4 in game two. In the Wednesday finale Chicago scored four runs in the second inning and managed 11 hits on the way to a 10-2 victory. Seiya Suzuki was the star of the show, logging two homers, five RBI, two runs and three hits. Matt Shaw added two hits, two runs, a walk and two RBI as well. 

As starter for Friday’s matchup, the Cubs are sending out Shota Imanaga. This year over two starts Imanaga is 1-0 with a 0.82 ERA and six Ks in 11.0 innings. Imanaga is 16-3 with a 2.78 ERA in 31 career starts. 

Why the Chicago Cubs will win

• The Padres have lost each of their last six games against the Cubs following a win.
• The home team has won nine of the Padres’ last 10 games.
• The Padres have failed to cover the run line in seven of their last eight games against the Cubs following a home win.
• The Cubs have covered the run line in four of their last five games.
• The Padres have trailed after 5 innings in each of their last three day games against National League opponents that held a winning record.

Why the San Diego Padres will win

• The Cubs have lost nine of their last 10 games against the Padres following a win.
• The Padres have won each of their last six games following a home win.
• The Cubs have failed to cover the run line in 11 of their last 12 home games against the Padres following a win.
• The Padres have covered the run line in eight of their last nine road games against NL Central opponents that held a winning record.
• The Cubs have trailed after 3 innings in four of their last five games against opponents that held a winning record.

Total Runs Facts

• Each of the Cubs’ last four games have gone OVER the total runs line.
• Four of the Padres’ last five games have gone UNDER the total runs line.
• The ‘Inning 1 UNDER 0.5 runs’ market has hit in eight of the Cubs’ last nine games against National League opponents.
• The ‘Inning 1 OVER 0.5 runs’ market has hit in five of the Padres’ last six games against NL Central opponents.

Cubs vs Padres Prediction 

I’ll lean toward the Cubs. Imanaga has a couple of starts under his belt already, with some pretty good results in both. He started out with a no-decision versus the Dodgers on March 18, posting 4.0 clean frames, no hits and four walks. Imanaga got a win over Arizona in his last game with one earned in 7.0 frames. As for Vasquez, he did well against a struggling Braves team in his 2025 debut, logging 6.0 clean innings, four hits and four walks. 

Chicago has been pouring in the runs lately, with four or more in six of their last seven games. The Cubs put up a combined 35 runs in three games during a sweep of the A’s, so if those numbers hold Imanaga won’t have to do much here in order to notch a victory.