The U.S.-Spain best-of-five series features three Top 12 singles players and three Top 10 doubles players. Ferrer is the highest-ranked among those nominated for singles matches while the United States has world No. 1 doubles team of the Bob and Mike Bryan.
The series will be played on a red clay court in Gijon and the Spaniards excel on clay. Ferrer is 19-4 in Davis Cup play, including 14-0 on clay, while Nicolas Almagro, Spain's other singles player, is 7-1.
Ferrer draws Sam Querrey, No. 26 in the world, in Friday's first singles match. They are 1-1 against each other but Querrey is 1-4 lifetime in Davis Cup matches -- all of which were played on clay courts.
The other singles match has 10th-ranked John Isner playing Almagro, who is ranked 12th. Isner is 7-3 in Davis Cup action on clay courts. Almagro won their only previous meeting, a tight four-setter at Wimbledon in 2011.
The schedule has a doubles match Saturday in which the Bryan brothers are to play Marcel Granollers and Marc Lopez. Lopez, like the Bryans, is a doubles specialist and ranked eighth.
The singles players swap opponents for Sunday's matches with the marquee match of Ferrer versus Isner first up, followed by the Querrey-Almagro match.
The winner of the U.S.-Spain semi moves into the Davis Cup finals Nov. 16-18 against either Argentina or the Czech Republic.
Spain, which beat Argentina in last year's final, has won five Davis Cup championships, all of which have some since 2000. The United States owns a record 32 titles with the most recent coming in 2007.