Bolton outmuscled Liverpool to inflict a third consecutive away league defeat on Rafael Benitez's side.
Reina has had an uncertain start to the season
Sam Allardyce's team went ahead with a disputed goal after Jose Reina was wrongfully penalised for handball.
Playing his 750th league game, Gary Speed inflicted maximum punishment on Liverpool as he arrowed in a free-kick.
Bolton extended their lead when Ivan Campo thumped a header against the bar and over the line from Kevin Davies' cross early in the second half.
Liverpool struggled on their league travels in Benitez's first season in charge and having picked up just one point away from home during this campaign they are again faltering outside of Anfield.
Bolton might have been fortunate with that first goal, but once they were ahead the way they defended suggested they were never going to relinquish their lead.
Both goalscorers typified that grit as they both made important defensive interventions as Liverpool threatened.
In the first half, Speed got back to tackle Jermaine Pennant, while after Campo had scored his goal, the former Real Madrid player was soon stretching to stop Jamie Carragher's pass reaching Luis Garcia.
Prior to Saturday, Benitez had been concerned about Bolton's physical approach and it was not long before he was expressing his frustration as his team were unsettled by the home side's tactics.
Abdoulaye Faye was booked for a crude tackle on Steven Gerrard, while Dirk Kuyt was left with a bloody head after he was involved in a clash of heads with the Bolton defender.
Liverpool's pain was further increased when they fell behind in controversial circumstances.
Reina was penalised for handling outside of his area, though television replays showed the Spaniard released the ball when he was clearly inside in his box.
Reina was made to pay for linesman Andy Halliday's mistake as Speed's low left-footed shot flew into the corner of the net.
The former Villarrel goalkeeper has had an uncertain start to this season and in trying to save Speed's free-kick he made the strange decision to dive in the space his wall was protecting as the ball went the other way.
Speed's strike was Bolton's only direct shot at goal in the first half.
Nicolas Anelka should have got a shot on target earlier but he delayed too long allowing Sami Hyppia to recover after he slipped allowing the Frenchman a chance to run at goal.
Either side of Speed's goal, Liverpool had chances to score.
Alonso's sweetly-struck volley hit the base of the post, while Jussi Jaaskelainen reacted quickly to beat away Gerrard's powerful shot.
If Bolton had been unable to conjure up an attack in the opening 45 minutes they proved quicker off the mark after the break.
On 51 minutes Davies delivered a cross from the right that was met by Campo with a thumping header that rebounded off the bar and over the line with Reina well beaten.
Bolton manager Sam Allardyce:
"The performance nullified them. We closed down, worked hard and had a gameplan and we frustrated Liverpool for all of the game really.
"What half-chances they did get, people were prepared to die to stop the ball going in the back of the net.
"We might have been a bit fortunate with the free-kick but we've taken advantage of it."
Liverpool manager Rafael Benitez:
"It's clear that a mistake has been made.
"Pepe let go of the ball inside the area and then kicked it outside.
"The linesman was in a bad position. I knew at the time it was a mistake but what can you do?"
Bolton: Jaaskelainen, Hunt, Meite, Faye, Ben Haim, Davies, Campo, Nolan, Diouf (Giannakopoulos 87), Speed, Anelka (Vaz Te 84).
Subs Not Used: Walker, Tal, Fojut.
Booked: Faye, Speed.
Goals: Speed 30, Campo 51.
Liverpool: Reina, Finnan, Hyypia, Carragher, Riise, Pennant (Luis Garcia 59), Sissoko (Zenden 75), Alonso, Gerrard, Kuyt (Crouch 49), Bellamy.
Subs Not Used: Dudek, Agger.
Ref: P Dowd (Staffordshire).