Tonga will return to BT Murrayfield for the first time since 2001, when the hosts won a pulsating match 43-20.
The two nations have played each other twice since then, with a win apiece in Aberdeen in 2012, and Kilmarnock two years later.
The teams have faced each other twice since then, both in Scotland, with Tonga winning in Aberdeen in 2012 and Scotland triumphing in Kilmarnock in 2014.
Covid-19 put paid to Scotland’s planned summer test series, with matches against England A, Romania, and Georgia all cancelled, and the Autumn Nations Series will be used to help the Dark Blues prepare for the 2023 Rugby World Cup, where Tonga could be among their opponents in Pool B.
Scotland will also welcome Australia, South Africa, and Japan to BT Murrayfield over the course of the Autumn Nations matches on consecutive weekends in November.
Tonga meanwhile face England at Twickenham the following weekend.
Scottish Rugby Chief Executive Mark Dodson said: “Following Scotland’s disrupted summer campaign we are pleased to be able to welcome Tonga to BT Murrayfield as part of our Autumn Nations Series.
“I’d like to thank Tonga Rugby CEO Peter Harding and the Tongan Rugby Union for their proactivity in working with us to secure this fixture to ensure we can give fans, players and coaches another test match to enjoy in 2021.
“Matches with Tonga are always competitive and physically demanding games and we feel this is the ideal way for our Autumn Nations Series to kick off and we look forward to welcoming Tonga back to Scotland.”
Tonga Rugby Union CEO Peter Harding added: “Both Unions have worked well together to generate an exciting event. Edinburgh is one of the great rugby destinations and BT Murrayfield is always a special venue.
“The intention of the ‘Ikale Tahi is to always walk toward the challenge of playing the best teams as often as we can and the exciting team currently playing under Gregor Townsend certainly provides a challenge.”
Tickets will be priced from £16 for adults and £11 for under-18s. Briefs go on sale from Monday, August 2.