The incident occurred during the second quarter, when Metcalf could be seen getting into an exchange with a Lions fan wearing a blue wig at Detroit's Ford Field.
The confrontation ended with Metcalf apparently striking the fan with his fist before walking away.
The Detroit supporter did not appear to be hurt, and responded to Metcalf's blow by raising his arms aloft in celebration.
It was not immediately clear what caused the confrontation, which rapidly went viral across social media.
The incident echoed a flashpoint involving Baltimore Ravens quarterback Lamar Jackson earlier this season.
Jackson shoved a Buffalo Bills fan during a week one defeat.
Jackson was not punished for that incident, which was initiated by the fan in question who was later ejected and banned from the Bills' Highmark Stadium.