Publisher Bethesda made the announcement at its press conference at the Electronic Entertainment Expo, also known as the E3 games show, in Los Angeles.
It also showed off a remake of iconic game Doom – out in Spring 2016 – and Dishonored 2.
Both Fallout 4 and Dishonored 2 will feature playable female characters.
On Tuesday, E3 will open its doors to the trade, press and around 5,000 members of the public.
Bethesda was the first of the major game publishers to hold an E3 event.
“I thought it was strong,” said Rob Crossley, UK editor of Gamespot, who was at the event. “It was robust. I think they had a lot to show.”
The company had shared a trailer for Fallout 4 earlier this month, but gameplay sequences were shown for the first time on Sunday.
A companion game called Fallout Shelter, which is played on a mobile application, was also announced.
In what was billed by Bethesda as a highly customisable environment, players can select a female lead character.
Dishonored 2 also features a female lead character – news which was greeted with cheers in the audience at Hollywood’s Dolby Theatre.
“I think it’s a really strong move, and I think it deserves a lot of credit,” said Mr Crossley.
“Over the past few years we’ve seen a growing understanding and acceptance that the industry needs to be more inclusive in how it welcomes women into games.”
Also getting a first-showing at the event was a remake of iconic series Doom, the game which defined the first-person shooter genre when it was released in the early nineties.
Marty Stratton, executive producer at Id Software, introduced a gameplay run-through of the new title.
In a nod to the original game, weapons such as the Super Shotgun and Chainsaw were demonstrated in a highly-violent scene in keeping with the series’ style.
A multiplayer mode was also shown off, including Doom Snapmap, a tool for creating modifications to the game, including custom-designed maps.
A special store will show off users creations for others to try out.