Bills vs. Patriots and Other Week 5 Over/Under Games to Target in Fantasy Football

High point totals mean opportunity, and several key matchups stand out as potential fantasy goldmines in Week 5.

Sep 28, 2025; Foxborough, Massachusetts, USA; New England Patriots quarterback Drake Maye (10) looks to throw against the Carolina Panthers during the first half at Gillette Stadium. Mandatory Credit: Brian Fluharty-Imagn Images | Brian Fluharty-Imagn Images

Week 5 of the NFL season is already upon us, and the challenge of setting lineups and finding an edge in fantasy football only becomes greater than the week before.  

While talent and matchups always matter, one of the most reliable indicators of fantasy potential comes from the betting market. High over/unders signal expected scoring, and more points on the board generally translate to more opportunities for fantasy production. Every touchdown and red-zone trip boosts the chances for quarterbacks, running backs, receivers, tight ends and even kickers to deliver starter-worthy numbers. 

This week’s slate offers several matchups with enticing totals. A handful of contests stand out as potential fantasy goldmines, making them worth targeting when finalizing lineups. Below are the games, along with some included fantasy football analysis and advice. 

*Over/under totals obtained from FanDuel Sportsbook* 

Detroit Lions @ Cincinnati Bengals (O/U: 49.5)

Even with Jake Browning under center for the Bengals, this game has the potential to be a shootout. Both offenses boast explosive skill players, and both defenses have proven to be exploitable thus far. Jared Goff is a strong start against a Bengals defense that’s surrendered the seventh-most passing yards per game (240.7). His pass-catchers are locked in, as Amon-Ra St. Brown is a must-start, and Jameson Williams is an intriguing flex option with lots of upside. Sam LaPorta also belongs in lineups, as Cincinnati is among the league leaders in fantasy points awarded to tight ends. On the ground, both Jahmyr Gibbs and David Montgomery are starters in this contest. Gibbs brings PPR juice while Monty maintains a substantial workload on the ground after coming off a monster performance against the Ravens. For Cincinnati, Jake Browning is more of a two-QB/Superflex option, but his weapons make him viable. Ja’Marr Chase and Tee Higgins are both automatic plays in a projected high-scoring affair, while Chase Brown is worth starting with volume on his side in what could be a back-and-forth game script.

Sep 28, 2025; Detroit, Michigan, USA; Detroit Lions wide receiver Amon-Ra St. Brown (14) catches a touchdown pass during the first half against the Cleveland Browns at Ford Field. Mandatory Credit: Lon Horwedel-Imagn Images | Lon Horwedel-Imagn Images

Quarterbacks:

Jared Goff - Start 

Jake Browning - Two QB/Superflex Play 

Running Backs:

Jahmyr Gibbs - Must Start 

David Montgomery - Start 

Chase Brown - Start 

Wide Receivers:

Ja’Marr Chase - Must Start 

Tee Higgins - Start 

Amon-Ra St. Brown - Must Start

Jameson Williams - Start  

Tight Ends:

Sam LaPorta - Start

New England Patriots @ Buffalo Bills (O/U: 49.5)

This AFC East clash has sneaky shootout potential, as Josh Allen and the Bills are the hottest team in the NFL, and Drake Maye is finding his rhythm with the Patriots. James Cook is a must-start, while Rhamondre Stevenson and TreVeyon Henderson are flex-level plays against a Buffalo front that has allowed the second-most yards rushing per game (164.3) through four weeks. However, their timeshare makes things tricky. Stefon Diggs is a strong start in his revenge game, especially after posting his best game as a Patriot last week. Khalil Shakir is emerging as a reliable WR3/flex in this offense with touchdowns in back-to-back contests. Keon Coleman is a deeper flex dart throw, but Patriots wideouts like Kayshon Boutte and DeMario Douglas should remain on the bench. At tight end, Dalton Kincaid remains a strong start, while Hunter Henry should sit. Buffalo is one of the toughest defenses against tight ends so far this season. 

Sep 28, 2025; Orchard Park, New York, USA; Buffalo Bills running back James Cook (4) runs for a gain past New Orleans Saints cornerback Isaac Yiadom (27) during the first quarter at Highmark Stadium. Mandatory Credit: Gregory Fisher-Imagn Images | Gregory Fisher-Imagn Images

Quarterbacks:

Josh Allen - Must Start

Drake Maye - Start 

Running Backs:

James Cooks - Must Start 

Rhamondre Stevenson - Flex  

TreVeyon Henderson - Flex

Ray Davis - Sit 

Wide Receivers:

Stefon Diggs - Start 

Khalil Shakir - Start 

Keon Coleman - Flex

Kayshon Boutte - Sit 

DeMario Douglas - Sit 

Joshua Palmer - Sit 

Tight Ends:

Dalton Kincaid - Start  

Hunter Henry - Sit

Las Vegas Raiders @ Indianapolis Colts (O/U: 48.5)

This game may not carry the same name recognition as others on the slate, but Daniel Jones and the Rams are loaded with fantasy appeal, and Ashton Jeanty and the Raiders have potential to shine in favorable matchups. Jones continues to be a viable start given his rushing floor and the matchup, while Geno Smith is better left on the bench until Las Vegas’ passing game shows more consistency. In the backfield, Jonathan Taylor is a must-start centerpiece who should see plenty of work regardless of game script, and Jeanty makes for a strong start for the same reason, especially coming off his three-touchdown performance against the Bears. At wide receiver, Michael Pittman Jr. is a reliable starter with steady volume, while Jakobi Meyers can be deployed as a flex option. Tre Tucker and Josh Downs don’t project for enough targets to trust in lineups this week. At tight end, both Brock Bowers and Tyler Warren are strong starting options as both are dynamic weapons in each team’s respective offense. 

Sep 28, 2025; Paradise, Nevada, USA; Las Vegas Raiders running back Ashton Jeanty (2) catches the ball for a touchdown during the first quarter against the Chicago Bears at Allegiant Stadium. Mandatory Credit: Stephen R. Sylvanie-Imagn Images | Stephen R. Sylvanie-Imagn Images

Quarterbacks:

Daniel Jones - Start 

Geno Smith - Sit 

Running Backs:

Jonathan Taylor - Must Start 

Ashton Jeanty - Start 

Wide Receivers:

Michael Pittman Jr. - Start 

Jakobi Meyers - Flex 

Tre Tucker - Sit 

Josh Downs - Sit 

Tight Ends:

Brock Bowers - Start 

Tyler Warren - Start 

Washington Commanders @ Los Angeles Chargers (O/U: 47.5)

This matchup profiles as a fantasy-friendly environment, as Jayden Daniels’ return from injury is anticipated. Both quarterbacks are viable starters. Daniels’ rushing ability makes him a strong play if he’s healthy, while Justin Herbert should thrive against a Washington secondary that has given up splash plays all season. In the backfield, Omarion Hampton is the safest start thanks to his volume, while Jacory Croskey-Merritt is a deeper flex option. Chris Rodriguez Jr. and Jeremy McNichols can be left on the bench. At receiver, Terry McLaurin (if active) is a starter, even with his recent struggles. Deebo Samuel also belongs in lineups due to his versatility. Quentin Johnston has established himself as the biggest breakout player in 2025. Therefore, he should stay in lineups this week. Keenan Allen and Ladd McConkey are both flex considerations in what should be a pass-heavy script. Finally, Zach Ertz should be benched, as the Chargers have guarded the tight end position well thus far in 2025. 

Sep 28, 2025; East Rutherford, New Jersey, USA; Los Angeles Chargers wide receiver Quentin Johnston (1) celebrates after scoring a touchdown during the second quarter against the New York Giants at MetLife Stadium. Mandatory Credit: Vincent Carchietta-Imagn Images | Vincent Carchietta-Imagn Images

Quarterbacks:

Jaden Daniels (Q) - Start 

Justin Herbert - Start 

Running Backs:

Omarion Hampton - Start 

Jacory Croskey-Merritt - Flex 

Chris Rodriguez Jr. - Sit 

Jeremy McNichols - Sit 

Wide Receivers:

Terry McLaurin (Q) - Start 

Deebo Samuel - Start 

Quentin Johnston - Start 

Keenan Allen - Flex

Ladd McConkey - Flex 

Tight Ends:

Zach Ertz - Bench 

San Francisco 49ers @ Los Angeles Rams (O/U: 46.5)

The NFC West clash between the 49ers and Rams may have a slightly lower total than some other shootouts this week, but the offensive stars on both sides make it a strong fantasy target. Brock Purdy remains a solid start thanks to his efficiency and weapons, while Matthew Stafford is viable as well in what could be a competitive, back-and-forth game. Christian McCaffrey is, as always, a must-start centerpiece, and Kyren Williams deserves the RB2 nod with his heavy usage in both phases. At receiver, Puka Nacua is also a lineup lock, as he’s currently the WR1 in PPR formats. Davante Adams still commands fantasy relevance, as he’s reached the end zone in three straight games. Ricky Pearsall (if healthy) is a start-worthy option given his growing role, while Jauan Jennings is a flex play in deeper leagues. At tight end, Jake Tonges is worth a flyer in deeper formats with George Kittle still sidelined, as the Rams are middle-of-the-pack in terms of fantasy points allowed to tight ends.

Sep 28, 2025; Santa Clara, California, USA; San Francisco 49ers running back Christian McCaffrey (23) runs after a catch against Jacksonville Jaguars linebacker Yasir Abdullah (56) during the second half at Levi's Stadium. Mandatory Credit: Darren Yamashita-Imagn Images | Darren Yamashita-Imagn Images

Quarterbacks:

Brock Purdy - Start 

Matthew Stafford - Start 

Running Backs:

Christian McCaffrey - Must Start

Kyren Williams - Start 

Blake Corum - Sit 

Brian Robinson Jr. - Sit 

Wide Receivers:

Puka Nacua - Must Start 

Davante Adams - Start 

Ricky Pearsall (Q) - Start 

Jauan Jennings - Flex 

Tight Ends:

Jake Tonges - Deeper League Play