Villarreal left it late to take the initiative in the Europa League semi-final, prevailing 1-0 over Liverpool thanks to Adrian Lopez's last-minute strike.
Adrian, who scored in Atletico Madrid's Champions League semi-final win over Chelsea in 2014, was on hand to potentially deal out further misery to a Premier League side, while Liverpool will need another inspired Anfield night next week.
Liverpool set pulses racing with a remarkable comeback and injury-time triumph over tournament favourites Borussia Dortmund in the previous round – a stark contrast to this largely cagey encounter.
Visiting manager Jurgen Klopp started without a conventional centre forward, leaving Daniel Sturridge as an unused substitute despite Divock Origi's injury absence and Liverpool lacked cutting edge despite a controlled display in midfield, led by the excellent James Milner.
Nominal attacking spearhead Roberto Firmino had a shot touched against the post by home goalkeeper Sergio Asenjo after Villarreal striker Cedric Bakambu came similarly close to his 10th Europa League goal of a stunning campaign.
It was left to fellow forward Adrian to crown a slick counter-attack – Bruno's lofted pass in behind Kolo Toure stylishly collected by Denis Suarez, who calmly rolled across goal to leave his team-mate with a simple finish.
Liverpool might have opened the scoring on their first attack of note in the fifth minute, but Joe Allen shot too close to Asenjo.
Former Tottenham forward Roberto Soldado sent a bouncing shot across Simon Mignolet's goal and the Liverpool keeper plunged to his left in the 21st minute to keep out Tomas Pina's 20-yard drive.
Toure got in the way of a sweetly struck Bruno effort and Alberto Moreno regained his footing to deflect Mario Gaspar's follow-up behind.
Bruno was Villarreal's main source of creativity and he found Soldado for the striker to spin into space and curl wide right-footed three minutes before the break.
The hosts almost led a minute into the second half when Bakambu rose to above Dejan Lovren to head Jonathan dos Santos' corner against the outside of the post.
Liverpool were operating with changed personnel by that stage, as Jordon Ibe replaced Philippe Coutinho at the break due to the Brazilian attacker feeling unwell.
The play became increasingly listless as a scrappy content passed the hour, although it was soon Liverpool's turn to test the upright.
Firmino collected a measured pass from his captain, Milner, and fired a low shot goalwards that Asenjo did well to tip against the base of his near post.
A robust challenge from Lucas Leiva on Pina prompted a seemingly furious touchline confrontation between Klopp and opposite number Marcelino – order soon restored as the German embraced his opposite number with a trademark chuckle.
Adam Lallana was incorrectly flagged offside as he stole in behind the Villarreal defence and Eric Bailly's pursuit of the England international resulted in him hobbling from the field.
Bakambu drew a late save from Mignolet and Moreno tore forward to blast over the break from the subsequent corner before Suarez and Adrian combined to show them how it was done.