Featuring the voices of Winona Ryder and Martin Short, the film tells the story of a boy who tries to bring his beloved dog back to life.
It will receive its European premiere at the event on 10 October and will be shown simultaneously at 30 other screens across the UK.
The festival will also host an Art of Frankenweenie show from 17-21 October.
Free to the public, the exhibition will feature original sketches drawn by Burton, props, sets and puppets to illustrate the work that went into bringing the animation to the big screen.
Technically-speaking, the film has been in the works for 28 years - since Burton first filmed the story as a young employee at Walt Disney Studios.
The live-action short, which starred Shelley Duvall and a young Sofia Coppola, was deemed too scary by the family-friendly company, who had planned to show it before a re-release of Pinocchio.
According to legend, Burton was fired as a result. The short film can currently be found as a bonus feature on the DVD version The Nightmare Before Christmas.
In contrast to Disney's original reaction, London Film Festival director Clare Stewart said the 2012, 3D version of Frankenweenie was a "perfect choice of opener".
"Funny, dark and whimsical, this gloriously crafted stop-motion 3D animation from Tim Burton playfully turns the Frankenstein story on its bolted-on head," she said.
"It's a film that revels in the magic of movies from one of cinema's great visionaries."
Burton, Ryder, Short and other voice actors Catherine O'Hara and Martin Landau are expected to attend the premiere.
It is the second time in recent years the festival has chosen a stop-motion animation film to open the gala.
Wes Anderson's The Fantastic Mr Fox, which featured the voices of George Clooney and Susan Sarandon kicked off the event in 2009.
The London Film Festival will run from 10 - 21 October.
The full programme for the event will be announced on 5 September.
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