Plug and Play Spain began operating in 2012 as the Spanish branch of the Silicon Valley startup accelerator Plug and Play. Founding partners Juan Luis Hortelano, Rubén Colomer and Juan Martínez launched it with Aquaservice CEO Alberto Gutiérrez and Plug and Play CEO Saeed Amidi, and by mid-2017 it had accelerated 72 startups across 10 programs with five exits, including Quolaw and Ducksboard.

In 2017 the founding team stepped back and the operation shifted from seed-stage acceleration toward vertical programs linking startups with large corporations. Its Spanish entity, Plug and Play Platform Spain, S.L., is registered in Paterna, and in 2025 Managing Director Borja Aznar led Plug and Play's southern Europe activity from Valencia, including a €20 million fund with EA Ventures.