Ryan Babel's header clawed a below-par Reds side back on level terms on the stroke of half-time, before second-half goals from Albert Riera and David N'Gog secured the points needed to knock Atletico Madrid off the top of the group.
Rafael Benitez's side could now be handed a slightly easier last 16 tie as they will be paired with a side who finished runners-up in their group.
The Reds were already assured of their place in the next stage so Benitez opted to rest the likes of Steven Gerrard, Xabi Alonso and Jose Reina in a much-changed starting line-up.
In a low-key opening to the game it was the home side who showed first when Diego Cavalieri was forced to palm away a powerful 20-yard strike from Timmy Simons after 16 minutes.
Liverpool were seeing plenty of the ball but looked short of ideas in the final third, with N'Gog and Babel both guilty of giving possession away cheaply.
PSV duly took advantage as they grabbed the lead in controversial circumstances after 36 minutes.
Liverpool felt the corner which led to the goal should have gone their way and the visitors' mood was not helped when Javier Mascherano failed to head the set-piece clear.
The ball dropped to Danko Lazovic and he steered a shot from the corner of the six-yard box under the diving keeper to the delight of the home fans.
Riera was booked for claiming there was a handball in the build-up to the goal and the perceived injustice seemed to inspire the Reds to up their efforts.
N'Gog wasted their best chance of the first half as he meekly headed a pinpoint Andrea Dossena cross straight at the keeper from 12 yards.
But first-half stoppage time brought an equaliser when a previously out-of-sorts Babel leapt highest to glance a lofted Lucas free-kick past the diving keeper from ten yards.
After the interval it was all Liverpool despite the home side knowing a win could see them qualify for the UEFA Cup via third place in the group.
N'Gog wasted a couple of half-chances before Riera settled the visitors' nerves with a stunning strike on 68 minutes.
The Spain winger light up a low-key night with a sensational left-foot shot from 25 yards which found the top corner past a flat-footed keeper.
Liverpool made sure of the points and top spot in the group when the previously anonymous N'Gog was played in on goal by a superb Robbie Keane through ball and he dispatched a low angled shot past the keeper from 15 yards.