Centrowitz will be joined by three-time Olympian Nick Willis of New Zealand in the men's race, and triple US champion Morgan Uceny will challenge Cain in the women's race in what has become the trademark event in the 107-year-old New York indoor meeting.
Cain, who recently broke her world junior indoor record for 1,000 metres, was originally announced for the 800 metres, but decided to change events.
"We felt Mary needs the experience of running in a competitive mile with a big pack before the USA Indoor Championships," said her coach, Alberto Salazar.
"The Wanamaker Mile will be the pre-eminent indoor mile race in the world this year so it will be great for Mary to continue to experience running in a large field against very good runners."
The Millrose Games is the second stop of the 2014 Indoor USATF Championship Series, which will conclude at the USA Indoor Track & Field Championship and world trials on February 22-23 in Albuquerque, New Mexico.
Willis also switched after initially planning to run in a special 2,000 metres race to honour Finland's Paavo Nurmi, who won gold medals at three Olympics and set a 2,000 metres world record at The Armory in 1925.
"I was scheduled to run the 2,000 but I ran a 3:53 mile in New Zealand in January," said Willis, the 1,500 metres silver medallist at the 2008 Beijing Olympics.
"So I thought if I'm ever going to have a chance to run a fast time in the mile this might be my best opportunity on one of the fastest tracks in the world," Willis said.
Featured in the Paavo Nurmi 2,000 metres is the all-time leader of Wanamaker Mile winners Bernard Lagat, whose eighth victory in 2010 put him one-up on the great Irish miler, Eamonn Coghlin.
Lagat has registered US records over two miles and 5,000 metres in the past two Millrose Games and is targetting another US best in the 2,000.
Two-time US Olympian Wallace Spearmon leads the field in another seldom-run distance, the men's 300 metres.
"I love the 300 metres distance," said Spearmon, who has won world championship medals in the 200 metres and 4x100 metres relay.
Spearmon set the 300 metres indoor world best in a blistering 31.88 seconds in 2006.