Professional football is the ultimate week-to-week game. You cannot simply rely on last year’s data or preseason expectations to make winning roster determinations, and sometimes you can't even rely on what happened last week because weekly opponent shifts can turn a player's outlook upside down. Finding the best fantasy football matchups and properly navigating away from the worst fantasy football matchups requires analyzing current defensive tendencies, injuries, and game scripts in real-time. To stay ahead of the curve as you set your lineups for fantasy football matchups in Week 10, let's examine where the true edges lie.
Looking back at our calls from last week, our sharpest instincts paid off. Trusting players like Brock Purdy and standout rookie Jonah Coleman proved to be a league-winning move for managers, while successfully avoiding quarterbacks like Bryce Young and Gardner Minshew spared countless fantasy rosters from major heartbreak. For full disclosure, we were wrong on starting Quinshon Judkins, however, as offensive coordinator Todd Monken has leaned into a heavier split favoring Dylan Sampson alongside a pass-heavy game plan. Let's apply those lessons to this week's slate.
Best Fantasy Football Matchups for Week 10
Brock Purdy, QB San Francisco 49ers vs. Dallas Cowboys
Purdy finds himself in an elite spot this week against a Dallas Cowboys defense that has struggled to contain efficient passing attacks. Purdy’s processing speed and the weaponry, which now includes veteran receiver Keenan Allen, surrounding him in San Francisco create one of the best fantasy football matchups on the board. Dallas has allowed substantial yardage through the air over recent weeks, and with Kyle Shanahan scheming players wide open in the middle of the field, Purdy is primed for a massive statistical outing that makes him a locked-in QB1 for fantasy football matchups in Week 10.
Chuba Hubbard, RB Carolina Panthers vs. New Orleans Saints
All aboard the Chuba Chuba Train! Hubbard gets a dream scenario squaring off against the New Orleans Saints. New Orleans has had glaring vulnerabilities against physical, north-south runners who can exploit gaps in their front seven. Hubbard’s workload and guaranteed touches make this one of the best fantasy football matchups for running back-needy managers. Expect Carolina to feed Hubbard early and often to control the tempo, securing a high floor and massive ceiling.
Pat Freiermuth, TE Pittsburgh Steelers vs. Cincinnati Bengals
Yes, we are still targeting against Cincinnati with our tight ends. The position’s landscape can be a wasteland, but Freiermuth enters Week 10 with a phenomenal pairing against the Cincinnati Bengals. Cincinnati has consistently struggled to defend athletic tight ends over the middle, frequently surrendering chunk plays and red-zone targets to the position. Freiermuth remains a primary security blanket for his quarterback, locking him into the best fantasy football matchups tier for this week's slate.
Worst Fantasy Football Matchups for Week 10
Jordan Love, QB Green Bay Packers vs. Minnesota Vikings
People are going to hate me for this, but I am concerned about this week. While Jordan Love is a transcendent talent, facing the Minnesota Vikings defense on the road is a nightmare scenario for fantasy managers. Brian Flores' scheme specializes in confusing quarterbacks with disguised coverages and relentless pressure. This ranks as one of the worst fantasy football matchups of the week, making it wise to temper expectations or look for streaming alternatives if you have viable depth.
Chase Brown, RB Cincinnati Bengals vs. Pittsburgh Steelers
Chase Brown has flashed explosive upside at times, but a divisional clash against the Pittsburgh Steelers presents a massive roadblock. So does the presence of Samaje Perine and excessive shotgun work. Pittsburgh’s front seven plays with extreme discipline and physicality, particularly at home, choking off rushing lanes. Because of the anticipated game script and defensive front, this qualifies as one of the worst fantasy football matchups for running backs in fantasy football matchups for Week 10.
Drake London, WR Atlanta Falcons vs. Kansas City Chiefs
Drake London is typically a weekly starter, but drawing a matchup against the Kansas City Chiefs defense, and specifically their locking secondary units, creates a tough ceiling. Kansas City excels at taking away an opponent's primary perimeter weapon. Facing bracket coverage away from home pushes this contest into the worst fantasy football matchups category, requiring caution before locking him into high-stakes lineups. Tough to sit him, so definitely temper expectations.
Fantasy Football Matchups to Target
Drew Lock, QB Seattle Seahawks vs. Las Vegas Raiders
Drew Lock steps into a pristine environment against a vulnerable Las Vegas Raiders defense that has struggled to generate consistent pass rush or lock down opposing wideouts. Seattle’s offensive scheme should allow Lock to push the ball downfield efficiently, making this one of the premier targets when evaluating fantasy football matchups Week 10. The game plan may go run-heavy given the match-up, but that will only open up the passing game more and take all the pressure off Lock. But it’s still him and Jaxon Smith-Njigba.
Ollie Gordon, RB Miami Dolphins vs. Indianapolis Colts
Volume is king, and we know he gets the volume. Gordon gets a fantastic opportunity to showcase his skill set against an Indianapolis Colts defense that has routinely leaked yards on the ground and should do so even more without DeForrest Buckner clogging the middle. Miami is expected to lean heavily into their ground game to establish control, making Gordon an outstanding player to target across season-long and DFS formats this week.
Fantasy Football Matchups to Avoid
Fernando Mendoza, QB Las Vegas Raiders vs. Seattle Seahawks
Probably the worst first-game matchup of all time, but the kid has to show us he belongs at some point, right? But starting a quarterback behind a shaky offensive line against Mike Macdonald’s ferocious Seattle Seahawks defense is a recipe for disaster. Seattle excels at confusing young or newly minted starters with complex defensive fronts. Fantasy managers should aggressively avoid starting Fernando Mendoza in fantasy football matchups Week 10.
Tony Pollard, RB Tennessee Titans vs. Jacksonville Jaguars
The explosiveness over the two games before the bye week has everyone buzzing, and the fact that he wasn’t traded at the deadline tells you just how much Robert Saleh and Brian Daboll are buying into him. But Pollard faces a stiff test against a Jacksonville Jaguars unit that has tightened up significantly against opposing run games. With divisional familiarity and potential negative game scripts looming, Pollard carries a suppressed ceiling, making him an easy fade as you finalize your starting lineups.