The 24-year-old has agreed a four-year contract at Craven Cottage with the club having the option to extend it by a further 12 months.
Cuenca, who has been capped by Spain up to under-21 level, began his career at Alcorcon and moved to Barcelona before joining Villarreal.
He made 37 appearances for the Yellow Submarine last term, helping them to finish eighth in La Liga and reach the last 16 of the Europa League.
The Cottagers completed the club record signing of Arsenal midfielder Emile Smith Rowe on Friday for an initial £27m.
Ryan Sessegnon has also returned to Fulham this summer on a two-year deal after his contract at Tottenham expired.
The west London side are also trying to sign Manchester United midfielder Scott McTominay, having made a second bid, believed to be worth £20m, for the 27-year-old Scotland international.