Sunday’s game will be the 26th regular-season meeting between the two with the Bills having won 10 of their previous 11 matchups.
The big storyline for the game is that Thaddeus Lewis is set to start at quarterback for Buffalo while E.J. Manuel recovers from injury.
Despite that, the Bengals will be weary of the Bills after being upset by the Cleveland Browns in Week 4. Doug Marrone's side has already toppled the Baltimore Ravens and will look to add Cincinnati to that list.
So, let's begin our preview of Sunday's game with six bold predictions for Week 6.
Thaddeus Lewis will hope to emulate Brian Hoyer when the Cincinnati Bengals visit in Week 6.
It won't be easy for the new Bills QB.
He's only seen one regular-season appearance (in 2012 for the Browns in a losing effort against the Steelers) and faces a tough defense with a chip on its shoulder.
After being embarrassed by the Browns in Week 4, the Bengals defense sacked Tom Brady four times, broke his TD pass streak and held him to under 200 yards passing.
Bold Prediction: 0 Points for Buffalo.
Fantasy owners rejoice!
C.J. Spiller may have played Thursday, but you might not want to start him this week.
He's likely to split carries fairly evenly with Fred Jackson as the Bills assess his health.
The Bengals held the Patriots running backs to under 100 yards last week after focusing on shutting down the run.
They'll almost certainly try and do the same this week, forcing Thad Lewis to air it out.
Bold Prediction: Under 30 Yards for C.J. Spiller.
Confidence is key.
Adam Jones has had a pretty good few days.
Last Sunday, he picked off a Tom Brady pass to seal a win for the Bengals over the Patriots in what was a pretty solid game for the resurgent cornerback.
Unsurprisingly, he's been busy off the field, too.
On Tuesday, he was found not guilty of assaulting a woman outside of a Cincinnati bar earlier this year, via Josh Katzowitz of CBS Sports.
Jones will be relieved to close the book on this chapter absolved of any damage to his recovering reputation.
He'll head into Week 6 with a clean slate and one of his best games of the year under his belt. It could set him up for a big day, and with Thad Lewis under center, Jones will fancy his chances.
Bold Prediction: Pacman gets a pick-six.
Given his recent performance, one TD pass might qualify as a bold prediction here.
However, Andy Dalton is about to turn it around, and he's going to do so against the league leaders in interceptions.
According to Josh Kirkendall of Cincy Jungle, "Dalton is currently on pace to throw a career-low 16 touchdowns and tie a career-high 16 interceptions, including his first red zone interception in his career on Sunday."
He seems to play best when the pressure is on him, and his seat continues to heat up despite the big win over New England.
If Dalton wants to quieten the critics, Buffalo could be the perfect place to do it.
Bold Prediction: Andy Dalton throws three TDs.
What's wrong with Andy Dalton and A.J. Green? Is there a communication problem? What is Green's body language saying about his relationship with Dalton?
These are just some of the many questions being asked about the QB/WR tandem.
They've struggled to get on the same page in 2013, and the Bengals have suffered for it.
I predict that they start to turn the corner in Week 6.
The Bills have a number of key injuries in their secondary, and Stephon Gilmore's status remains up in the air. If he's out, Green could have a fun afternoon.
Of the three aforementioned Andy Dalton TDs, Green will be responsible for two.
Bold Prediction: Two TDs for Green.
Carlos Dunlap has three sacks credited to him in 2013 so far.
On Sunday, he'll double that total.
It seems that the new contract has motivated the athletic DE, while he's also benefited from opposing offenses focusing on Geno Atkins.
He didn't record a sack in the win against New England, but Ben Volin of The Boston Globe cited him as one of the biggest standouts:
"He was disruptive in the run game (five tackles and a forced fumble) and controlled Sebastian Vollmer for much of the game."
Dunlap is fast becoming the player the Bengals hoped he would, and it's shown through the first five weeks of 2013.
Bold Prediction: Sorry Thad, three sacks for Dunlap.