The 31-year-old Powell has agreed a two-and-a-half-year contract and will leave Sale after two seasons next month.
Powell won the last of his 23 Wales caps in 2012 and toured South Africa with the British and Irish Lions in 2009.
The last high-profile rugby union player to switch to league was former Wales captain Gareth Thomas who joined Crusaders in 2010.
"This is a good signing for us, reminiscent of Scott Quinnell who became a highly successful Wigan forward before returning to Union as an even better player," Wigan chairman Ian Lenagan told the club's website.
"Andy is a strong and powerful rugby player and I am certain he will be able to make the switch of codes successfully. We are delighted to get his signature and this is a coup for the Wigan Club to acquire a player of his talent and potential."
Powell said he had always been interested in playing rugby league.
"This is a fantastic opportunity for me and one I am really looking forward to," he said.
"I have always thought that a move to Rugby League could be an option for me at some point in my career and when I learned of Wigan Warriors' interest I was excited about the chance to make the switch.
"Wigan Warriors are the biggest name in Rugby League; they also have a rich history of Welsh connections over the years and are a huge name in the Principality."
- Sports & Recreation