The match appeared to be heading for a stalemate until substitute Adrian Lopez poked home two minutes into injury time.
It was less dramatic than Dejan Lovren's header against Borussia Dortmund two weeks previously - Jurgen Klopp's side still have the home leg to come - but frustrating nonetheless as they had appeared to have ground out a draw.
Going to the El Madrigal, where the hosts have now won all seven Europa League ties this season and are unbeaten in the competition since matchday one on September 17, was always going to be tough - but the Reds seemed to have done the hard work until a momentary lapse in concentration cost them.
Daniel Sturridge was on the bench again for Liverpool - a pattern repeated over four European matches now - despite his four goals in the last five games. Roberto Firmino was given the role as a nominal centre-forward.
While the Brazil international did a lot of the hard yards, pressing from the front as per his manager's instructions, he could offer neither the pace nor precision Sturridge has.
Klopp had urged his players not to waste that dramatic win over his former side two weeks ago and Joe Allen, on his first European start since November 26 and only his fourth in the competition this season, almost got them off to a flier.
Arriving into the penalty area at speed in the fifth minute he could only direct Adam Lallana's cross straight at Sergio Assenjo when a shot a yard either side of goalkeeper would have produced the breakthrough.
Without the focal point of Divock Origi, who injured ankle ligaments a week ago in the Merseyside derby but fortunately does not require surgery and could make a return before the end of the season, Liverpool were aimless in the final third.
Too often crosses were swung in at no one in particular, giving centre-backs Eric Bailly and Victor Ruiz an easy ride.
As a result Villarreal had the better chances with former Tottenham striker Roberto Soldado off-target with two shots at either end of the half, while Simon Mignolet got down well to parry Tomas Pina's low effort.
Villarreal right-back Mario Gaspar also had efforts snuffed out by Kolo Toure, continuing in central defence with Mamadou Sakho now officially suspended by UEFA for a failed drugs test - and Lovren.
The ineffectual Philippe Coutinho - reportedly being watched by Barcelona scouts - was replaced by winger Jordon Ibe at the break after feeling unwell but within 40 seconds of the restart Cedric Bakambu headed against the post from Jonathan dos Santos' corner.
Firmino, having kept himself onside, responded midway through the half with a shot which Asenjo tipped onto the upright - but that was as close as the visitors came.
Mignolet came to their rescue three minutes from time when Bakambu seized on Ibe's mistake while charging full-back Alberto Moreno ignored the unmarked winger from a quick counter-attack and instead fired into the side-netting.
But in added time substitute Lopez slid home after Denis Suarez had outpaced Toure.
Liverpool manager Jurgen Klopp insists he does not need to tell his players the importance of their Europa League semi-final first leg in Villarreal as they have more than proved their hunger for the competition.
After dramatically beating Borussia Dortmund in the previous round Klopp's side were immediately installed as favourites.
However, the Reds boss has stressed there has been no talk of a possible final appearance in Basle next month.
"It is important to understand my players came into a semi-final because they were always ready for the moment and never thought about the next round," he said.
"It is important I show the players the respect they earned, which means I don't need to speak to them about things they did well.
"We are here because we respected this tournament each round. There is no doubt from my side.
"Villarreal did the same until now so it is not about talking about the final.
"Villarreal show the highest level of football each week; the Spanish league is unbelievably strong and they play with such balance, structure and discipline and if you let them they play football."
Liverpool's European campaign has been at odds with their domestic form and Klopp is undefeated in 10 European games as manager - only Joe Fagan (12) has a longer unbeaten run in Europe from the start of a managerial reign than the German.
However, they will take nothing for granted in Spain and even a goalless draw away from home may not be enough for Klopp.
"If we are really good and should win why should I be satisfied with a draw?" he added.
"It is not one per cent preparation for the game thinking about the result.
"It is always about the performance. The result is always the result of the performance, nothing else.
"We only need to think about what we do and there is nothing to think about results."
Liverpool will again be without defender Mamadou Sakho as he remains sidelined - at his and the club's volition - after failing a drugs test.
Klopp insists they have handled it the best way they can after Sakho, Press Association Sport understands, decided not to submit his B sample for testing after a 'fat-burning' substance was detected in his system following last month's Europa League tie against Manchester United at Old Trafford.
"It is not that we could do anything or we could not force anything, we have to wait," said Klopp.
"Until now we did what we thought was right, there is nothing else to say."
There is an outside chance Sakho could escape with a severe reprimand if there are extenuating circumstances but team-mate Kolo Toure was banned for six months while at Manchester City in February 2011 for a doping violation after taking 'water tablets' on the recommendation of his wife and it appears Sakho is more likely to incur a similar suspension.
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