Match ends, Villarreal 1, Liverpool 0.
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.
BBC Radio 5 live summariser and former Reds defender Mark Lawrenson said: "Where did the left-back disappear to? Injury time at 0-0 in a Europa League semi-final - and he's probably 70 metres up the pitch.
"0-0 would have been a very good result. All of a sudden because of one aberration you're under pressure for the second leg."
Liverpool will have to score at least twice to go through in 90 minutes at Anfield, but Villarreal know an away goal would mean the Reds then need a minimum of three.
Reds lack attacking threat
Jurgen Klopp's Liverpool side were installed as favourites to win Europe's secondary club competition after their thrilling quarter-final win against Bundesliga club Borussia Dortmund.
Publicly the 48-year-old German insists there has been no thought about the possibility of reaching the final - but winning the trophy will cap an encouraging debut season with a place in next season's Champions League.
His predecessor, Brendan Rodgers, named an inexperienced side in the Reds' opening two matches in the competition, but Klopp has chosen stronger teams since arriving in early October.
However, he decided to play without a recognised striker at Villarreal, leaving England international Daniel Sturridge on the bench throughout - and the Reds offered little attacking threat.
Wales midfielder Joe Allen wasted the best chance in a tight first half, side-footing straight at home keeper Sergio Asenjo early on.
Further opportunities were rare, although Brazil forward Firmino - playing as Liverpool's most advanced player - thumped an angled 12-yard drive against the base of the right post.
Villarreal pay Hillsborough tribute
Liverpool were playing their first match since inquests concluded 96 Reds supporters who died as a result of a crush in the 1989 Hillsborough disaster were unlawfully killed.
Villarreal paid tribute to the victims by providing a banner - bearing the number 96 and Liverpool club slogan 'You'll Never Walk Alone' - for their fans to hold up before kick-off.
"We were very saddened by the Hillsborough tragedy and we planned events to show the solidarity and support which our club and our fans have with Liverpool and those who were affected," said the Spanish club.
'This race is not over'
Liverpool boss Jurgen Klopp:
"Of course I'm not too happy with the goal we conceded in the last second. Counter-attacking in the 92nd minute makes not much sense - but it is only the first leg.
"It is 1-0 and they have to come to Anfield where we know how strong we are. We had our moments, we defended really good. This race is not over.
"If we had enough players around the box it was no problem but they played this one chip ball over Kolo [Toure], I don't know where Alberto [Moreno] was in this moment but that was the only big mistake we made in this game and they scored with it."
Villarreal manager Marcelino:
"Until the final whistle you can score or concede a goal and this time we were lucky enough to score in the very last minute.
"We managed a good result but we don't know if it will be enough or not until the end of the tie.
"It was not an unfair result and we didn't beat Liverpool by being lucky."
Man of the match - Denis Suarez (Villarreal)
Seventh-placed Liverpool return to Premier League action with a visit to 15th-placed Swansea on Sunday.
The Reds look unlikely to earn Champions League qualification through the Premier League, sitting nine points behind fourth-placed Arsenal with four matches left, although they do have a game in hand on the Gunners.
Villarreal are better positioned to earn La Liga's final qualifying spot, holding a four-point advantage over Celta Vigo with three matches remaining.
- 2Pérez Martínez
- 24BaillySubstituted forMusacchioat 76'minutes
- 11Costa JordáBooked at 60mins
- 8J dos SantosSubstituted forCastillejo Azuagaat 72'minutes
- 18D Suárez
- 9SoldadoSubstituted forLópez Álvarezat 74'minutes
- 7García Sánchez
- 14Trigueros Muñoz
- 19Castillejo Azuaga
- 20López Álvarez
- 4K Touré
- 11FirminoSubstituted forBentekeat 90'minutes
- 10CoutinhoSubstituted forIbeat 45'minutes
- 44B Smith
- Damir Skomina
- Shots on Target
Second Half ends, Villarreal 1, Liverpool 0.
Goal! Villarreal 1, Liverpool 0. Adrián (Villarreal) right footed shot from the centre of the box to the centre of the goal. Assisted by Denis Suárez.
Substitution, Liverpool. Christian Benteke replaces Roberto Firmino.
Attempt missed. Alberto Moreno (Liverpool) left footed shot from the left side of the box is high and wide to the left.
Corner, Villarreal. Conceded by Dejan Lovren.
Corner, Villarreal. Conceded by Simon Mignolet.
Attempt saved. Cédric Bakambu (Villarreal) left footed shot from outside the box is saved in the bottom left corner. Assisted by Denis Suárez.
Attempt missed. Nathaniel Clyne (Liverpool) header from the centre of the box misses to the right. Assisted by Jordon Ibe with a cross.
Foul by Nathaniel Clyne (Liverpool).
Samu Castillejo (Villarreal) wins a free kick in the defensive half.
Foul by Joe Allen (Liverpool).
Adrián (Villarreal) wins a free kick in the attacking half.
Offside, Liverpool. Alberto Moreno tries a through ball, but Jordon Ibe is caught offside.
Delay over. They are ready to continue.
Substitution, Villarreal. Mateo Musacchio replaces Eric Bailly because of an injury.
Delay in match Eric Bailly (Villarreal) because of an injury.
Offside, Liverpool. Joe Allen tries a through ball, but Adam Lallana is caught offside.
Substitution, Villarreal. Adrián replaces Roberto Soldado because of an injury.
Offside, Liverpool. Kolo Touré tries a through ball, but Roberto Firmino is caught offside.