Perry will appear with Jon Stewart, Anderson Cooper and Jimmy Kimmel to help raise money for autism sufferers in New York later this month.
The singer will dedicate a performance of 'Firework' to one lucky audience member.
This year's Night of Too Many Stars theme is 'America Comes Together for Autism Programmes', which will see celebrities and public figures with opposite views unite to fight autism.
Stephen Colbert, Amy Poehler, 30 Rock's Tracy Morgan and Jack McBrayer, Julianne Moore, Jerry Seinfeld and Saturday Night Live stars Jason Sudeikis and Fred Armisen are also scheduled to attend.
Stewart has organised The Night of Too Many Stars biannually since 2006. The 2010 gala raised more than $3.2 million (£1.98m) for autism research and support.
The Night of Too Many Stars will be taped on October 13 at the Beacon Theatre, to air on Comedy Central on Sunday, October 21 at 8/7c.
Watch Tina Fey on the 2010 Night of Too Many Stars below: