She will be starring opposite Busted's Matt Willis, who has already featured in theatre productions Flashdance: The Musical, Footloose, Wicked, Little Shop of Horrors and Waitress.
Along with Tamsin Carroll and Felix Scott, they will make up the creepy play's fourth cast at London's Criterion Theatre, taking over the roles from 6 September to 8 January.
Whitmore, known for her TV work on MTV and Celebrity Juice, said: “I’m so excited to be making my West End debut playing Jenny in the next production of 2:22. Theatre has always been my first love and I can’t wait to get back on stage.
"I am a huge fan of the previous productions and delighted to be getting stuck in with rehearsals and working alongside such a hugely talented cast and team.”
Singer Willis, who has more recently carved out a theatre career, added: “I am beyond excited to be a part of this incredible show. I saw the production last year and absolutely loved it. I can’t wait for people to come and watch!”
Previous casts for 2.22 have included Lily Allen, Julia Chan, Hadley Fraser and Jake Wood; Stephanie Beatriz, James Buckley, Elliot Cowan and Giovanna Fletcher; and currently features Tom Felton, Mandip Gill, Beatriz Romilly and Sam Swainsbury.
Whitmore will be taking over Doctor Who star Gill's role as a woman who believes her new home is haunted, but her husband thinks it's nonsense.
They welcome a couple of old friends (Willis' character) for a dinner party where beliefs and scepticism clash, agreeing they'll all stay up until 2.22am when Jenny usually hears the same noises to find out for sure what is going on.
Playwright Danny Robins said: "I love the fact that, like Doctor Who, we keep regenerating and we have some truly thrilling performers here. How exciting is it to be looking forward to Laura Whitmore's stage debut?
"And Matt Willis has more than proved himself to be a brilliant, explosive actor in recent years. Felix and Tamsin make up our foursome - both absolutely epic talents.
"I have a feeling this is going to be a particularly spine-tingling incarnation of my play, so, if you haven't seen it already, come! If you have, come again!!! There's no better time than the autumn for a ghost story as the nights draw in... so come down to the Criterion and enjoy the ultimate spooky night out! We can't wait to unleash this new cast on you..."
Tickets are currently on sale at 222aghoststory.com.
Watch: ITV defends Laura Whitmore after hundreds of Ofcom complaints