The three-hour TV event on Thursday, May 21 will feature comedy acts and celebrity appearances, with the full line-up announced in coming months. Sienna Miller , Christina Aguilera and Mad Men's Jon Hamm are already backing the campaign.
"Red Nose Day is almost like a national holiday in the UK," said American Sniper star Miller.
"It's a day of real excitement as everyone looks forward to it and the entire country gets involved in some way. I'm thrilled it's coming to the US!"
NBC's president of alternative and late night programming Paul Telegdy, who previously worked on the UK version of Red Nose Day on the BBC, said: "It is a distinct honour to have our Red Nose Day efforts aimed toward assisting these exceptionally worthwhile charities.
"Our goal is to create an extraordinary broadcast that is entertaining while inspiring a level of goodwill and giving that will dramatically change the lives of those with the most immediate need."
Twelve charities working with children and young adults in the US and Africa will benefit from the charity event - broadcast from the Hammerstein Ballroom in New York City - and Comic Relief founder Richard Curtis said that he has long envisioned adapting the Red Nose Day telethon for US audiences.
"Experience has taught me how extraordinarily compassionate and generous Americans can be, and I've lived my life in awe of American comedy talent," he said.
"So putting those two things together will, I hope, create an amazing event that will make a massive difference to the lives of millions of children and their families," he added.
NBC will partner with Funny or Die to create original comedy content for the broadcast.
Comic Relief has raised over £1bn for causes around the globe since it was established 30 years ago.
Watch the video for Sam Smith and John Legend's Red Nose Day single 'Lay Me Down' below:
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