NFL Week 4 Betting Picks, Upset Picks & Analysis (2025)

Our favorite NFL Week 4 betting picks and upset predictions: including moneyline underdogs, point spread plays, and primetime game previews.

by Jason Lisk - Sep 26, 2025

(Photo by Cliff Welch/Icon Sportswire)

Welcome to our NFL Week 4 betting picks and upset predictions guide. This week, we’ll spotlight our favorite moneyline underdog plays along with other game-level bets that look like solid value opportunities.

We’ll also break down the Thursday and Monday Night Football matchups and point out potential betting angles to keep in mind.

Our full list of player prop best bets for Week 4 will be released separately on Saturday.

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NFL Week 4 Betting & Upset Picks: Published Content

When a new section is published or updated, we’ll add it to the list below.

• 9/25: NFL Week 4 Upset Picks
• 9/25: NFL Week 4 Game Picks
• 9/25: Thursday Night Football Breakdown

Thu Sept 25

NFL Week 4 Upset Picks

Each week, we highlight three moneyline underdogs with potential to win outright. These are higher-risk plays than spreads, but the payouts are bigger, sometimes two or three times your stake. You don’t need to win half your bets to profit. For example, hitting one of three at +200 puts you ahead.

Upset picks come with variance, so disciplined bankroll management is key. The odds listed reflect consensus numbers at publication, but always shop around for the best line.

Three Upset Picks for Week 4