The Reds created plenty of chances in an entertaining game, but were ultimately punished by two late goals for the home side.
Hulk fired Zenit into the lead with just over 20 minutes remaining when he arrowed into the top corner from range, before substitute Sergei Semak sealed victory for the Russians soon after.
It means Liverpool must secure a win by a three-goal-or-greater margin in the return meeting at Anfield next week or their aspirations of lifting silverware this season will be over.
Brendan Rodgers made three changes to his starting XI in Russia, with Raheem Sterling, Martin Skrtel and Joe Allen returning to the side in place of Jonjo Shelvey, Lucas Leiva and Daniel Agger.
The boss had used his pregame press conference to emphasize Liverpool’s determination to go all the way in the competition, while acknowledging Zenit would provide a stern test of his side’s aspirations.
And within 120 seconds, both sides had good chances to open the scoring. First, Hulk saw a stinging volley beaten away by a low stop from Pepe Reina. Meanwhile, at the other end, a Liverpool break resulted in Luis Suarez steering one inches wide of the far post.
Hulk was thwarted by the Reds goalkeeper again soon after, this time having a low drive from the edge of the box parried around the post.
With 16 minutes on the clock, Suarez spurned a golden chance to open the scoring when he raced clear of the Zenit defense and rounded Vyacheslav Malafeev after pouncing on a poor ball from Nicolas Lombaerts. However, his touch was too heavy and Lombaerts was able to recover and avert the danger.
The opening period was turning into something of a shootout between Suarez and Hulk — and the latter was next to threaten when he struck against the base of the post. With Reina grounded, the ball rolled agonizingly across the face of goal before the visitors cleared to safety.
In keeping with the game’s pattern, Suarez went close again five minutes before the break, this time flicking Sterling’s low cross the wrong side of the post from inside the six-yard box.
Liverpool had Zenit’s hearts in their mouths again shortly after the restart when Glen Johnson‘s surging run from halfway carried him into the area, but his prod towards goal was blocked by Malafeev’s sprawl.
Suarez then had them worried yet again when he curled just off target on the hour as the Reds began to threaten.
However, having enjoyed their best spell of the game, Liverpool found themselves behind when Hulk beat Reina from almost 30 yards with a powerful effort into the top corner on 69 minutes.
Zenit furthered their advantage just moments later as substitute Semak collected a deep cross completely unmarked at the back post and finished neatly.
It leaves Liverpool with it all to do in next week’s second leg — but history has proven anything is possible on European occasions at Anfield and Kopites will be hoping it’s another night to savour.
Liverpoolfc.com journalists’ man of the match: Steven Gerrard
Photo via Liverpoolfc.com