Brydon Carse, Paul Coughlin and Mitchell Killeen are all sidelined through injury, while Matthew Potts, Mark Wood and Ben Stokes are set to join up with the England squad to play Ireland at Lord's next week.
As a result the club have brought in Parnell, fresh from his time at the IPL with Royal Challengers Bangalore. He has previously played for five other counties - Sussex, Glamorgan, Kent, Northamptonshire and Worcestershire - as well as with Northern Superchargers in the Hundred.
He is Durham's second overseas signing specifically for the Blast alongside the Australia middle-order batter Ashton Turner, with David Bedingham likely to start the season on the bench.
"Wayne is an experienced international-level T20 bowler with a proven track record of delivering performances in franchise cricket," Marcus North, Durham's director of cricket, said.
"His experience of playing for and captaining T20 teams around the world will be valuable to us this season. He bowls left-arm pace and can provide runs down the order with the bat.
"He has played a lot of white-ball cricket in England and he comes straight to Durham on the back of a good stint in the IPL so he is ready to play when he arrives this weekend."
Parnell added: "I'm delighted to have this opportunity to play for Durham. I've thoroughly enjoyed my previous spells in England, and everyone speaks well of Durham.
"I know some of the lads in the dressing room so I'm hoping to fit straight in and use my experience to deliver some wins for the fans."