The actor will appear in a Thanksgiving episode as a divorced friend of Scott (Luka Jones) who attends the Brinkley family feast, reports Access Hollywood.
Sasso starred in last summer's hit The Three Stooges as Curly and also had a memorable stint on Fox's MadTV.
The Up All Night guest appearance reunites Sasso with his Three Stooges co-star Sean Hayes, who plays Ava's (Maya Rudolph) musical partner.
Arrested Development's Tony Hale will also feature in a future episode as a dentist who flirts with Reagan (Christina Applegate).
Up All Night airs Thursdays at 8.30/7.30c on NBC.
Watch Will Sasso in a MadTV sketch below: