Mayfield left the Browns in the offseason, following their move for DeShaun Watson, to join the Panthers, with the two sides to meet in Week 1.
"It's a great storyline," Mayfield said on Wednesday. "Obviously, there's history leading up to this week. [But] there's other games in the NFL that guys are playing their former team. It's just the excitement of leading up to Week 1 that is building that anticipation up. It's the familiarity."
The Browns drafted Mayfield first overall in 2018 but chose to replace him this offseason by acquiring Watson.
Speaking to reporters on Wednesday, Mayfield acknowledged that a game against so many former teammates can be a bit different, but he denied having any resentment towards the Browns organization.
"Any time you're playing guys you know, it makes it just more interesting, more fun," Mayfield said. "You get to smack talk with your buddies that you've been with for a little bit. You know how to poke and prod and get the best out of them.
"I'm looking forward to the opportunity.
"I'm grateful for the time I had in Cleveland," he said. "I started my career there. The fans there, it's a football town. As I mentioned multiple times it ended abruptly and unexpectedly, but we're here now.
"Everything happens for a reason. I'm rolling with the punches. I'm happy to be a Panther."
Mayfield won the job as the Panthers’ top quarterback over last year’s starter, Sam Darnold.
Mayfield was 30-30 starting under center for the Browns and helped give the franchise its first playoff win since the 1994 season.