The 19-year-old, who joined United last summer from Crewe, will move to the DW Stadium for the entire 2013-14 campaign, having made just two appearances in his first season at Old Trafford.
Latics boss Owen Coyle told the club's official website: "We're delighted to welcome Nick to Wigan Athletic, and thank Manchester United for allowing a player whom they have invested a large sum of money in and has incredible talent, to join us for the season.
"We're all excited to be offering him the opportunity to play football at a high level and for him to continue his development here at the club."
Powell became Coyle's 11th summer signing at the DW Stadium and Wigan left it late to make their 12th summer signing by bringing in Stoke defender Ryan Shotton minutes before the 11pm transfer window deadline.
The 24-year-old joins the Latics on loan and said: "It's been a whirlwind evening and we only found out really late about Wigan's interest. I can't wait to get going now and meet the players.
"As soon as I spoke to the gaffer and he told me how much he wanted me, I made up my mind and now I can't wait to get started.
"The club is obviously moving forwards and the squad here is really impressive. The competition for places is intense but that is what all players need and I'm going to do everything I can to win a place in the team.
"I played a big part in the European campaign for Stoke and that's something else that's really appealing about the club.
"I just want to say a big thanks to everyone at Stoke City.
"It's a club I've been at for 16 years so it's played a huge part of my life. Who knows what will happen in the future but for now I'm a Wigan Athletic player and I can't wait to get started."