A late Axel Witsel effort left Valencia's determined fightback in vain as the Belgian secured a 3-2 Champions League win for Zenit at the Mestalla on Wednesday.
After falling 2-0 down before the break thanks to a brilliant Hulk double, Valencia battled back in the second period and restored parity, only for Witsel to leave the hosts ruing their defensive naivety in their Group H opener.
The hosts endured their first taste of frustration after just two minutes, as Joao Cancelo saw his attempt come back off the post and Hulk capitalised shortly after with a neat finish.
A trademark Hulk screamer just before the break doubled the visitors' lead, but Witsel inadvertently diverted a Cancelo cross past his own goalkeeper early in the second period to give Valencia encouragement.
Andre Villas-Boas' men were forced to withstand intense pressure after that goal and half-time substitute Andre Gomes netted a deserved equaliser for Valencia in the 73rd minute.
But Zenit had the last laugh, as Witsel fired a low drive inside the post from distance just three minutes later, leaving Valencia despondent upon their return to Europe's elite competition.
Fresh from clinching their first win of the season against Sporting Gijon at the weekend, Valencia looked full of confidence early on, with Sofiane Feghouli finding joy against left-back Domenico Criscito.
Valencia's first chance unsurprisingly came down that very same flank, but it was right-back Cancelo who went close, sending a low 25-yard effort against the post in the second minute.
Zenit had no such misfortune seven minutes later, though, as Danny led a breakaway and fed Hulk into the left side of the area, with the Brazilian duly applying a powerful finish across Jaume Domenech to open the scoring.
The home side continued to dominate despite falling behind, but clear-cut opportunities were something of a rarity, as inaccurate crosses and blocked shots started to frustrate fans.
Valencia eventually tested Yuri Lodygin two minutes before the break, but the Russian goalkeeper held on to Dani Parejo's header.
And Zenit capitalised shortly after, as Artem Dzyuba knocked down a lofted pass from the back and Hulk subsequently blasted into the roof of the net in emphatic fashion from 30 yards.
Nuno Espirito Santo introduced Paco Alcacer and Gomes at the break, but it was the lively Cancelo who helped pull one back for the hosts in the 54th minute, as Lodygin was inexplicably beaten at his near post by the full-back's cross which took a wicked deflection off Witsel.
Spurred on by the goal, Valencia's dominance only became greater and Parejo went agonisingly close to levelling in the 63rd minute, sending a half-volley just wide from the edge of the area.
The equaliser did eventually arrive courtesy of Gomes, however, as the Portuguese midfielder skipped past one tackle and then beat the suspect Lodygin from a tight angle.
But Witsel bailed his goalkeeper out a few minutes later, finding the left-hand corner from 25 yards to secure a battling win for Zenit.
