Stoke will have to win in the Mestalla next week if their European adventure is to continue after Valencia claimed a 1-0 win in the first leg of their Europa League last-32 clash at the Britannia Stadium.
Mehmet Topal netted the only goal of the game in the 36th minute with a 30-yard screamer that gave Asmir Begovic absolutely no chance.
Sofiane Feghouli also hit the post in the second half while Stoke, who have lost their last four Barclays Premier League games, were limited to half-chances.
Potters boss Tony Pulis described the tie as one of the greatest occasions in the club's history and there was certainly a big difference between the teams in terms of experience, with Valencia playing their 100th game in the Europa League or UEFA Cup compared to Stoke's 15th.
The cliche about European teams normally involves asking how they would fare on a wet evening in Stoke, and the hosts were quick to test their opponents, with Jon Walters benefiting from a misplaced header but firing well wide of target.
Valencia's class was beginning to tell as the half wore on although there was a certain irony that their opening goal after 36 minutes came from a thundering 30-yard shot from Topal that left Begovic pawing at thin air.
Feghouli then fired just wide as Valencia turned the screw but Stoke were almost level moments later when a peach of a cross from Jermaine Pennant was met by Peter Crouch's acrobatic volley that flew just over the crossbar.
Cameron Jerome and Ryan Shotton came on for Crouch and Marc Wilson, but Stoke almost found themselves two behind in the 71st minute when Feghouli again found space down the right.
He jinked his way into a shooting position in the middle of the box and was desperately unlucky to see the ball bounce off the inside of the post and onto Begovic but not find its way into the net.
Stoke continued to probe and Robert Huth stabbed a shot wide from Matthew Etherington's corner before Shotton's 25-yard effort deflected off a defender but Vicente Guaita recovered just in time as the visitors settled for a one-goal victory.