Stubbs will be available for the majority of the competition following his commitments with Mumbai Indians in the IPL.
He was part of the Manchester Originals squad that reached the final of the Hundred last summer, but this will be his first experience playing county cricket.
"We are extremely pleased to have secured the signing of Tristan Stubbs," Marcus North, the club's director of cricket, said.
"At 22, he already has experience playing for South Africa and in major T20 franchise leagues around the world where he has produced some world-class performances."
Stubbs was the most expensive player signed at the inaugural SA20 auction last year and was part of the Sunrisers Eastern Cape squad that won the title earlier this month, despite an underwhelming season with the bat.
"I can't wait to get over to Durham and meet up with my new team-mates," he added. "Having played in England last summer I know how much the fans love their cricket so it should be a really fun and successful summer."
Durham are one of five counties who have never won the Blast, and last reached Finals Day in 2016. Last season, they won only three games as they finished second-bottom of the North Group.
They have also brought in Ollie Robinson, Nathan Sowter, Brandon Glover and Bas de Leede over the winter and will expect a better showing under new coach Ryan Campbell.