Former world No. 1 Moya and Fish, who won the silver medal in the 2004 Olympics, will meet in the first match. Roddick, also a former world No. 1 and now ranked second to Roger Federer, goes against Nadal in the second match.
Spanish captain Jordie Arrese said he chose Nadal over veteran Juan Carlos Ferrero as his second singles player for "tactical and technical reasons."
Ferrero, who also was once the world's top-ranked player, has been bothered this year by illness and injuries.
The U.S. captain is Patrick McEnroe.
The singles players will switch opponents in the final matches Sunday.
The United States has won the Davis Cup 31 times. Spain's only win was in 2000.