That's because they will officially turn from Oklahoma teammates to NFL rivals on Sunday.
Mayfield will be making his second start at quarterback for the Cleveland Browns, and his former top target in Andrews will be looking to make plays as the Baltimore Ravens' top pass-catching tight end.
"When we get into the game, he’ll be trash-talking," Andrews said. "He’ll say his few words to me and I’ll say something to him. It’ll be fun."
Mayfield and Andrews were considered to be the top players at their positions in college football last year.
Mayfield won the Heisman Trophy for the game's top overall player. Andrews received the John Mackey Award, which is given to college football's most outstanding tight end. They were both first-team All-Americans.
With his ability to get open and outrun defensive backs, Andrews became Mayfield's favorite target. They connected on 62 passes for 958 yards and eight touchdowns.
In the draft, Mayfield was selected No. 1 overall by Cleveland, and Andrews was taken in the third round (No. 86 overall) by Baltimore.
"It will be weird for sure, seeing that guy you’ve competed with for the last four years and playing against him," said Andrews, who has 10 receptions for 119 yards and a touchdown. "Just knowing how dangerous he is and how passionate he is for the game is a scary thought. But, at the same time, I have a ton of trust in our teammates to go against him."
Andrews hasn't been surprised by how Mayfield has fared in his first two NFL games.
Two weeks ago, Mayfield came off the bench to rally the Browns from 11 points down and beat the New York Jets, 21-17, for the franchise's first victory in 635 days. Last Sunday, he threw for 295 yards and two touchdowns in a 45-42 overtime loss in Oakland.
"He’s a competitive guy," Andrew said. "He’s only going to continue to get better with all the reps he’s going to get."
Ravens defensive players might ask Andrews whether he has any inside information on his college quarterback.
"I’m sure they’ll be wondering a bit about him," Andrews said. "Our defense is stacked. They’ll be just fine."
Mayfield will see another familiar face on the Ravens. Orlando Brown Jr., a backup offensive lineman for Baltimore, lined up at left tackle for Oklahoma last year.
With Brown, Mayfield never got sacked from his blind side last season.
"It will definitely be different. I’m used to having him in my backfield," Brown said. "I want the best for him. Hopefully, he doesn’t play his best game against us."
Asked if he has any good stories about Mayfield, Brown laughed and said, "Nothing that I would be willing to share anyway."
Brown remains in contact with Mayfield, but he said Andrews is closer with him. Andrews refers to Mayfield as one of his best friends and said he talks routinely with Mayfield.
"We’re rooting for each other," Andrews said. "But we have two games a year against each other. Other than that day, we’re good friends."