The two teams will compete in a series of pop culture games such as Trading Faces, Dance in Your Pants, Song Sung Wrong, Smash the Buzzer, I Love a Charade and Celebrity Name Game.
The episode will help raise money for Red Nose Day which fights to end child poverty.
NBC will partner with the nonprofit behind Red Nose Day, Comic Relief US, to air the sixth annual Red Nose Day primetime event on May 21 at 8 p.m. EDT.
"So many people are facing profound loss and more uncertainty than ever before. All of us at Hollywood Game Night wanted to do something positive and helpful during this current crisis and since we're of no use to the heroic medical professionals, a special episode of the show for such a worthy cause seemed like the next best thing," Lynch said in a statement.