A Friday night match between Ireland and Wales in Dublin will kick off the Autumn Nations Cup, an eight-team tournament involving the Six Nations sides, plus Fiji and Georgia.
The competition will be played over four weekends, starting on 13 November.
The other opening games are England v Georgia and Italy v Scotland on the Saturday, then France v Fiji on Sunday.
England, Ireland, Wales and Georgia are in Group A, while Group B contains Scotland, France, Italy and Fiji.
The Autumn Nations Cup starts two weeks after the final round of the 2020 Six Nations is completed and finishes on the weekend of 5-6 December.
On that final weekend, teams will face the side in the equivalent finishing position in the other group.
England v Ireland on 21 November will be shown on Channel 4, as will Ireland v Wales and Ireland v Georgia. Amazon Prime will provide coverage of the tournament's other fixtures.
Rugby Football Union chief executive Bill Sweeney said he remained "cautiously optimistic" that fans will return for the internationals.
"We look forward to hearing from the Department for Digital, Culture, Media and Sport on the detail following yesterday's government update. We will provide more information in due course," he added.
England will play their home matches at Twickenham, Scotland at Murrayfield and Ireland at the Aviva Stadium, but the venues for Wales, France and Italy's home games are still to be decided.
Prior to England's men taking on France on 21 November, England's women will play the second of two internationals against France in a Twickenham double-header.
Simon Middleton's side will have played the French the previous weekend, before facing Italy over the weekend of 31 October.
Japan were initially set to join the tournament before travel restrictions as a result of the coronavirus pandemic forced their withdrawal.
"While the challenges presented by the Covid-19 pandemic made the traditional autumn Test window unfeasible, we remained determined to deliver a unique and compelling tournament proposition which would ensure world-class rugby for our fans globally, and competitive matches for players, unions and federations," said Six Nations chief executive Ben Morel.
While there had been talks regarding South Africa's involvement, it has been confirmed Georgia will take Japan's place, a boost for Los Lelos as they battle for exposure and experience against the established rugby union nations.
"We are especially pleased to be joined by Fiji and Georgia and expect them both to be tremendous additions to the competition," added Morel.
Autumn Nations Cup fixtures (all times GMT)
Ireland v Wales, 13 November, 19:00
Italy v Scotland, 14 November, 12:45
England v Georgia, 14 November, 15:00
France v Fiji, 15 November, time TBC
Italy v Fiji, 21 November, 12:45
England v Ireland, 21 November, 15:00
Wales v Georgia, 21 November, 17:15
Scotland v France, 22 November, 15:00
Scotland v Fiji, 28 November, 13:45
Wales v England, 28 November, 16:00
France v Italy, 28 November, 20:00
Ireland v Georgia, 29 November, 14:00
Georgia v TBC, 5 December, 12:00
Ireland v TBC, 5 December, 14:15
Wales v TBC, 5 December, 16:45
England v TBC, 6 December, 14:00
All times GMT