Wales will launch their 2018 autumn Test series by tackling Six Nations rivals Scotland in Cardiff on November 3.
The countries open this season's Six Nations with a Principality Stadium clash on February 3.
And they will face each other again nine months later with Scotland becoming Wales' first tier-one northern hemisphere opponents since the four-match autumn series began 17 years ago.
The November encounter will see the Doddie Weir Cup played for. Former Scotland and British and Irish Lions lock Weir revealed last year that he is suffering from Motor Neurone Disease.
The match kicks off an extended November campaign for Scotland, who will also play three fixtures at Murrayfield against Fiji, South Africa and Argentina.
"Scotland will be an entirely different prospect outside of the Six Nations Championship, and this is a rare chance for a much broader base of supporters to experience a match of this magnitude," WRU chief executive Martyn Phillips said.
"We need four international matches in our autumn calendar in order to provide vital funds for the future sustainability of the game in Wales.
"Scotland's visit is the result of some innovative thinking from the national squads, rugby management and marketing teams of both nations."
The Scottish Rugby Union has also confirmed a three-match summer series in the Americas with games lined up against Canada, the United States and Argentina. Venues are still to be confirmed.
Scotland head coach Gregor Townsend said: "Facing Wales on the road is an exciting prospect for our players as we begin the final of year of preparations for Rugby World Cup 2019.
"Four Test matches in four weeks is a very similar challenge to the one that we will face in Japan.
"This additional contest in the autumn will allow us to expose more Scotland players to international rugby and will support our preparations to face three huge matches at Murrayfield later that month, and beyond."
The WRU says it will shortly announce Wales' three other autumn Tests for this year.