And he'll face someone Chicago is familiar with, new Bills backup Mitchell Trubisky.
Three days after Fields racked up 175 all-purpose yards and two touchdowns in his preseason debut against the Miami Dolphins, Chicago's first-round pick landed on the injury list Wednesday with groin soreness.
Limited to light throwing on Wednesday, Fields returned to practice on Thursday and will see significant action against the Bills, according to head coach Matt Nagy, who plans to play veteran Andy Dalton for at least a quarter and a half before turning to Fields.
"I think yesterday giving Justin the day off to help him was good, and he feels good," Nagy said. "We want to sacrifice that day of practice to be able to get him right for Saturday."
The Bills will take a different approach to the game.
Buffalo coach Sean McDermott told reporters that Pro Bowl quarterback Josh Allen will not play at Soldier Field and that Trubisky -- the second overall pick in the 2017 NFL draft by Chicago -- will get the starting nod.
"We just want to continue to grow overall, and Mitch, obviously, new to our system, I think he's off to a really good start, and obviously overall as an offense, we want to continue to grow, too," McDermott said.
Trubisky was Chicago's most polarizing athlete from 2017 to '20. The quarterback, who turns 27 on Friday, helped guide the Bears to the playoffs in 2018 before things went downhill. After the Bears opted not the exercise Trubisky's fifth-year option, he signed a one-year, $2.5 million free-agent deal with Buffalo to serve as Allen's backup.
"Mitch is going to be focused, he's going to be doing his thing on Saturday," Nagy said. "But again, we understand that there's the business side and then there's the personal side. And the respect that we have for him as both a person and as a player, I think everybody here has that for him, all his teammates and coaches. We wish him nothing but the best.
"When the game's going on, we're going to do everything we can to stop him. When the game's over, we're going to, you know, be friends and have good stories. So that's the part of life in the NFL for all of us, but it is a relationship business, and I think it's important that everyone understands that on our end we care about him as a person. And we know that he's going to compete his tail off all the time to do well at quarterback."