As we enter Week 6 — one third of the way through the season, several teams are scrambling to plug holes at quarterback — from Ravens reeling without QB Lamar Jackson to the Browns starting rookie QB Dillon Gabriel again.
We've dug through every NFL game on the Sunday main slate to bring you our best Week 6 predictions in one place. We'll highlight the best matchups for QB, RB, WR, and TE to find the top PrizePicks NFL picks and NFL DFS matchups this week.
The 49ers sit at 4–1, but will once again start Mac Jones, who continues to struggle in place of an injured Brock Purdy. Rookie Dillon Gabriel is set to build on a promising start across the pond, earning another opportunity to start in a pivotal Week 6 matchup on the road in Pittsburgh.
Veteran Joe Flacco has been traded to the Cincinnati Bengals to start in place of injured Joe Burrow, while Cooper Rush is expected to get the call once again for the Ravens.
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This PrizePicks Cheat Sheet for Week 6 is your ultimate resource for the top player picks for NFL DFS, projections to target, and matchup insights for the Week 6 main slate.
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NFL Week 6 Predictions & Cheat Sheet for PrizePicks, NFL DFS
Find the top Week 6 predictions, picks, matchups to target, and players to target for NFL Week 6 below in the PrizePicks Cheat Sheet, including player picks for NFL DFS.
- Best RB Matchups: Week 6
- Best WR vs. CB Matchups to Target: Week 6
- Best OL/DL Mismatches to Target: Week 6
- Best TE Matchup for Week 6
Best RB Matchups to Target: Week 6
Here are the top RB picks for NFL Week 6, including PrizePicks projections to target for NFL DFS.
Raiders RB Ashton Jeanty vs. Titans
The Tennessee Titans have quietly become one of the NFL’s worst teams at defending the run. They are:
- Allowing 4.99 yards per carry, fifth worst in the league.
- Giving up a league-high 10 rushing touchdowns.
- Surrendering 146.8 rushing yards per game, third worst in the NFL
This horrible run defense now faces rookie first-round pick Ashton Jeanty. After a slow start behind one of the NFL's poorest offensive lines, Jeanty has found his rhythm. Jeanty currently ranks:
- Top 10 in carries (82)
- Top 10 in rushing yards (349)
- Top 10 in rushing touchdowns (2)
What’s most impressive is Jeanty’s efficiency and elusiveness, attributes that made him a star in college and are now translating to the NFL. Per PFF, he ranks:
- 2nd in missed tackles forced (22)
- 7th in yards after contact per carry (3.82)
- 3rd in explosive runs (12 carries of 10+ yards or more)
Week 6 PrizePicks Pick: Ashton Jeanty – 76.5 Rush Yards
Packers RB Josh Jacobs vs. Bengals
The Cincinnati Bengals are also struggling mightily against the run. Their defense ranks:
- 8th-worst in rushing yards allowed per game (132.2)
- Tied for 5th in rushing touchdowns allowed (6)
- 5th-worst in yards after contact allowed (320 total YAC)
Up front, defensive tackle TJ Slaton has been a major liability, ranking 107th out of 118 interior defensive linemen in run-stopping, per PFF.
That’s welcome news for Josh Jacobs, who continues to be the workhorse for the Packers offense. Jacobs ranks:
- 4th in the NFL in rushing touchdowns (4)
- 8th in carries (80)
- 23rd in rushing yards (266)
Although Jacobs is averaging a modest 2.92 yards per carry, against a Bengals defense that’s leaking yards after contact thus far, there's a path to success.
Week 6 PrizePicks Pick: Josh Jacobs – 80.5 Rush Yards
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Best WR vs. CB Matchups to Target: Week 6
Here are the top WR vs. CB matchups to look to for NFL Week 6, including PrizePicks projections to target for NFL DFS.
Chargers WR Quentin Johnston vs. Dolphins CB Jack Jones
Injury note: Quentin Johnson was limited in Friday's practice with a hamstring injury and is officially listed as questionable. If he sits out, expect Ladd McConkey to get more looks, as well as Tre Harris, both against a vulnerable Dolphins secondary.
The Miami Dolphins secondary has been one of the league’s worst to start the 2025 season, contributing to their disappointing 1-4 record.
CB Jack Jones has been particularly poor in coverage, ranking 93rd out of 106 qualified corners, according to PFF. When targeted, he is surrendering a 116.4 passer rating, which places him 41st worst in the NFL, while also allowing 11.4 yards per reception — a glaring vulnerability on the outside.
Opposite him this week is Chargers wideout Quentin Johnston, who has finally emerged as a reliable threat in 2025. Johnston ranks:
- 5th in the NFL in receiving touchdowns (4)
- 7th in receiving yards (377)
- 4th in routes run (189)
- 12th in total receptions (26)
- Averaging 14.5 yards per reception
Johnston has already exceeded his PrizePicks yardage projections of 58.5 in four of five games this season.
Most importantly, Johnston has earned the full trust of QB Justin Herbert, becoming a vertical threat and reliable possession receiver. Johnston is second on the Chargers in target share with 23.3%, and No. 1 in weighted opportunity rating (61.1%), per FTN.
Week 6 PrizePicks Pick: Quentin Johnston – 58.5 Receiving Yards
49ers WR Kendrick Bourne vs. Bucs CB Zyon McCollum
Kendrick Bourne is re-establishing himself as a key weapon for the 49ers, especially with the offense currently battling several injuries. With Ricky Pearsall not expected to play, Jauan Jennnings limited in practice, both and George Kittle on injured reserve, Bourne should be a top target for the 49ers once again.
Last week, Bourne had a breakout performance, posting:
- 10 receptions
- 142 receiving yards
- 12.9 yards per target
- Improving to a 108.2 passer rating when targeted on the season
He now gets a matchup against Bucs corner Zyon McCollum, who has struggled all season. Per PFF, McCollum has allowed:
- A 126.6 passer rating when targeted
- 11.6 yards per reception
- 17 receptions through just 5 games
Best OL/DL Matchups to Target: Week 5
Here are the top OL vs. DL mismatches in NFL Week 6 games, including PrizePicks projections to target for NFL DFS based on the mismatches.
Rams DL > Ravens OL
The Los Angeles Rams boast one of the NFL’s most dominant defensive lines, ranking fourth in run stop win rate and 10th in pass stop win rate, per ESPN.
OLB Jared Verse, at just 24 years old with limited experience, has quickly become a rising star. He currently ranks top 10 in total pressures (23), first in QB hits (10), and 25th in hurries (11) across the league. OLB Byron Young adds to the damage with 20 pressures (17th in the NFL) and 6 sacks, which ranks second among all edge rushers.
On the interior, DE Kobie Turner ranks 4th out of 119 interior defenders via PFF and has collected 9 total pressures and 7 hurries.
The Ravens’ offensive line is struggling so far in 2025. LT Ronnie Stanley will return from an ankle injury, but RT Roger Rosengarten has allowed 7 pressures (56th among tackles) and committed 2 penalties in 260 snaps.
On the interior, LG Andrew Voorhees has allowed 10 pressures (78th) and 1 sack (56th) over 261 snaps. C Tyler Linderbaum has also been underwhelming, giving up 9 pressures, which ranks 40th among centers.
Add a struggling offensive line to a team missing its MVP QB Lamar Jackson, and the Ravens offense could have their hands full vs. the Rams defense.
Week 6 PrizePicks Pick: Derrick Henry – 67.5 Rush Yards
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Jaguars DL > Seahawks OL
The Jacksonville Jaguars have quietly become one of the most disruptive front sevens in football.
DE Josh Hines-Allen is playing at an All-Pro level, ranking 5th in pressures (26), 3rd in QB hits (8), and 6th in hurries (17). Former No. 1 overall pick Travon Walker adds 14 pressures, 10 hurries, and 2 sacks, making the Jaguars’ edge tandem one of the most potent in the league.
On the interior, veteran DE Arik Armstead has turned back the clock with 3 sacks, 10 hurries, and 14 pressures, ranking top 15 among interior linemen.
Seattle’s offensive line has been a liability to start 2025, ranking 22nd in pass blocking grade, per PFF. RG Anthony Bradford ranks 76th out of 79 guards in pass-blocking and has already allowed 11 pressures and 1 sack.
LG Greg Zabel has surrendered 8 pressures, 3 QB hits, and 1 penalty. C Jalen Sundell hasn’t been much better, giving up 4 pressures and drawing 2 penalties, placing him 33rd among centers.
Week 6 PrizePicks Pick: Sam Darnold – 239.5 Pass Yards
Best TE Matchups for Week 6
Here are the top TE picks for NFL Week 6, including PrizePicks projections to target.
Colts TE Tyler Warren vs. Cardinals
Former Penn State tight end and first-round pick Tyler Warren is off to a terrific rookie campaign. He ranks:
- 4th among all tight ends in targets (31)
- 4th in receptions (23)
- 1st in receiving yards (307)
Despite slowing a bit in recent weeks after an explosive start, he's averaging 13 yards per reception, ranking 3rd among all tight ends, and he’s top five in yards after contact per reception (7.0).
The Cardinals’ linebacker group has been a liability in coverage. Akeem Davis-Gaither is allowing a 126.2 passer rating when targeted, while Mack Wilson isn’t much better, surrendering a passer rating over 100 when in coverage.
As a result, tight ends have routinely gone more than their receiving yards projections against this defense. The last three tight ends to face Arizona — AJ Barner, Gunnar Helm, and Ja’Tavion Sanders, all exceeded their projected receiving yardage totals.
Warren has averaged over six targets per game, with 70+ yards receiving in three of four games — only missing that number in two blowout wins vs. the Titans and Raiders.
Week 6 PrizePicks Pick: Tyler Warren – 51.5 Receiving Yards
Patriots TE Hunter Henry vs. Saints
Hunter Henry continues to produce at an elite level for the Patriots, especially with rookie QB Drake Maye — 5th in total EPA (45.38) — relying on him as a consistent safety valve. Henry ranks:
- 2nd among tight ends in yards per reception (14.7)
- 3rd in passer rating when targeted (135.1)
- 6th in receiving yards (252)
- 3rd in receiving TDs (3)
Despite a shaky Patriots offense, Henry’s been a consistent bright spot and remains a focal point in the passing attack.
On the other side, the New Orleans Saints’ linebackers have been consistently beaten in coverage. Pete Werner has allowed a 134.5 passer rating, and veteran Demario Davis has also surrendered a passer rating over 124 when targeted.
The Saints have given up the 27th most fantasy points to tight ends, averaging 56.6 yards and 0.8 TDs to opposing tight ends per game.
Week 6 PrizePicks Pick: Hunter Henry – 42.5 Receiving Yards
Make NFL Week 6 Predictions on PrizePicks
Week 6 is loaded with matchups to target and tons of excitement in every game. As we reach the one-third mark of the season, Week 6 is another opportunity to win real money on PrizePicks.
Use these NFL Week 6 predictions and cheat sheet to sharpen your takes and build out your winning Lineups for Sunday's Week 6 slate.
PrizePicks is the simplest way to win real money with your NFL predictions all season long. Pull up the NFL board, pick at least two players, predict More or Less on their projections — like yards or receptions — and win real money when you’re right.
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