Liverpool’s ambitions of reaching their first European final in almost a decade suffered a blow as Villarreal netted an injury-time winner in the first leg.
After a first half of few chances, Cedric Bakambu’s header clipped the Reds upright shortly after the break.
Liverpool went closest when Roberto Firmino’s low shot hit the post.
The Reds looked set for a creditable draw in Spain until they switched off to allow substitute Adrian Lopez to tap in Denis Suarez’s low cross.
Despite the dramatic winner, the Europa League semi-final still remains delicately poised before next Thursday’s return leg at Anfield.
The winners will face either Spanish holders Sevilla or Ukrainian side Shakhtar Donetsk, who drew 2-2 in their first leg, in the Swiss city of Basel on 18 May.
Could late defensive lapse prove costly?
Liverpool have not reached a European final since losing to AC Milan in the 2007 Champions League showpiece, but a stoic display at La Liga’s fourth-placed team looked set to leave them a home win away from ending that barren run.
However, the Premier League side lost their defensive discipline in the final few seconds – and it could prove crucial.
Left-back Alberto Moreno wandered up field, leaving the space for former Manchester City youngster Suarez to exploit before squaring to Lopez for the easiest of finishes.