Ferrer defeated Isner 6-7 (3-7), 6-3, 6-4, 6-2 by breaking Isner's serve six times. It is uncharacteristic for an opponent to record so much success against Isner's serve but Ferrer won 42 percent of the points when receiving serve. He had two breaks in each the second and fourth sets and one each in the first and third.
Isner, who made 95 unforced errors in a five-set loss Friday to Nicolas Almagro, had 70 unforced errors Sunday versus Ferrer.
Ferrer's win meant Sunday's fifth match of the series would not be played.
Ferrer beat Sam Querrey in four sets Friday. The three wins in singles gave Spain a 3-1 lead in the best-of-five series. The Americans' point came Saturday when the world No. 1 doubles team of Bob and Mike Bryan was a four-set winner over the Spanish team of Marcel Granollers and Marc Lopez.
Spain will now advance to meet Czech Republic in the Davis Cup finals Nov. 16-18, after they bested Argentina later Sunday.
Spain topped the Czech Republic in the 2009 finals.