Wales's first four-match November series was held in 2001.
"Scotland will be an entirely different prospect... a rare chance for a much broader base of supporters to experience a match of this magnitude," said Welsh Rugby Union chief executive Martyn Phillips in a statement on Friday.
The Celtic duo will also compete for the Doddy Weir Cup, donated by the Welsh Rugby Union, with contributions from the match set to be given to the 'My Name'5 Doddie Foundation'.
The cup is named after former Scotland international Doddie Weir, who is battling motor neurone disease and seeking to help fellow sufferers.
The two teams will play for the trophy every time they meet under similar circumstances in the future.
Wales last hosted Scotland, outside of the Five or Six Nations Championship, in a friendly in August 2003 and the Scots last won in Cardiff in a Six Nations match in 2002.
(Reporting by Aditi Prakash in Bengaluru; Editing by Toby Davis)
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