L.A. to Vegas, about an airline crew and their passengers which stars McDermott, is set to debut on Fox during the midseason.
Mulroney will guest-star on an episode of the series as Capt. Steve, a charismatic pilot who will rival McDermott's Capt. Dave, Entertainment Weekly reported.
The pairing of the actors comes after McDermott and Mulroney have endured jokes over the years of how they share a similar look and name. Mulroney previously appeared in an episode of Saturday Night Live where he poked fun at his similarities to McDermott.
Mulroney last starred in the short-lived CBS series Pure Genius while McDermott was last seen in two short-lived CBS dramas including Hostages and Stalker.