The holiday special, titled "John Mulaney & the Sack Lunch Bunch," will premiere on the streaming platform on Christmas Eve.
The show will mark a departure from the comedian's typical offering, with "John Mulaney & The Sack Lunch Bunch" taking the format of a children's variety show that will include sketches and musical numbers.
"I'm John Mulaney and I am a 37-year-old man. The Sack Lunch Bunch is a group of children ages 8 to 13 who are more talented than me," Mulaney said of his latest project in a statement.
The musical children's special aims to "recapture the magic of that bygone television era when children sang songs about their feelings with celebrity guests on funky outdoor sets."
Among them are musician David Byrne, Tony Award winner André De Shield, "Orange is the New Black" actress Natasha Lyonne, award-winning actress Annaleigh Ashford and actor Jake Gyllenhaal.
"The result is a collage of Broadway-caliber showstoppers, comedy sketches for all ages, meditations on the unknown from children and adults, and a papier mache volcano. It's funny, musical, joyous, anxious and surprisingly profound," Mulaney teased.
As Vulture pointed out, "John Mulaney & The Sack Lunch Bunch" will also find the comedian reconnecting with some of his former "Documentary Now" collaborators, including director Rhys Thomas and composer Eli Bolin.
In addition to "John Mulaney & The Sack Lunch Bunch," the Emmy-winning comedian has previously teamed with Netflix for his and Nick Kroll's "Oh, Hello on Broadway" as well as his "Kid Gorgeous at Radio City," which was filmed during his 2018 sold-out run at New York's Radio City Music Hall.
This holiday season, Mulaney is not the only celebrity presenting his own Christmas special.
Earlier this month, country superstar Kacey Musgraves announced that her own star-studded variety show will premiere on Amazon Prime Video on November 29.
"The Kacey Musgraves Christmas Show" will find the hitmaker performing both classic and original holiday songs alongside guest artists such as Camila Cabello, Lana del Rey, Zooey Deschanel, James Corden, Troye Sivan and more.