The former Baltimore Ravens running back was handed the ban after footage of him punching his then-fiancee in February was released in early September.
Rice was initially handed a two-game suspension before the NFL decided to take action again following the release of the footage by TMZ.com.
The NFLPA wants a neutral arbitrator to hear the appeal, not commissioner Roger Goodell and his staff.
A hearing date needs to be set within 10 days and the NFLPA said an employee cannot be punished twice if all relevant facts were available to the NFL when it first banned Rice.
"Today, the NFL Players Association formally filed an appeal of the indefinite suspension of Ray Rice by the NFL," the association said in a statement.
"This action taken by our union is to protect the due process rights of all NFL players.
"The NFLPA appeal is based on supporting facts that reveal a lack of a fair and impartial process, including the role of the office of the commissioner of the NFL.
"We have asked that a neutral and jointly selected arbitrator hear this case as the commissioner and his staff will be essential witnesses in the proceeding and thus cannot serve as impartial arbitrators."