Fallout 4, the first addition to the series since 2010, will be available on Xbox One, PlayStation 4 and PC.
The hugely anticipated title has not yet been given a release date, but developer Bethesda said more details would be shared later this month.
Drug references in a previous version of the game led to it being temporarily banned in Australia.
Content in Fallout 3 had to be amended to appease regulators, and the game was given a 15+ age rating. Fallout 4 has a provisional 18+ rating.
Fallout 3 was the first in the series to be in a 3D "open world" - meaning the player was free to roam the game's environment of a devastated Washington DC.
As was widely rumoured, Fallout 4's open world will be set in Boston.
A trailer broadcast on Wednesday set up the game's storyline - one in which a nuclear war has destroyed civilisation.
A dog features heavily in the trailer, suggesting the animal may be a controllable character.
"We know what this game means to everyone," said game director Todd Howard.
"The time and technology have allowed us to be more ambitious than ever. We've never been more excited about a game, and we can't wait to share it."
Rob Crossley, UK editor of Gamespot, said he did not expect Bethesda to drift too far from the winning formula of Fallout 3.
"I wouldn't be shocked if the Fallout 3 formula with a new lick of paint would satisfy everyone.
"Fallout 3 wasn't the most handsome game in the world, it was a bit rough round the edges, and so a version with modern visuals could be enough.
"But there needs to be a level of innovation. I'd expect some new elements, but it won't steer too far from the template.
"They're not going to reinvent the wheel."
More details about the game will be announced ahead of video games conference E3, which takes places in Los Angeles later this month.
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A new instalment in the best-selling post-apocalyptic video game series Fallout has been confirmed.