The victory sees the Blaugrana make the best-ever start in the Spanish top-flight's 113-year history, surpassing the mark set by Radomir Antic's Real Madrid side of the 1991-92 season, while Messi's exploits, his 83rd and 84th goals in 2012, moved him to within one of Gerd Muller's 85-goal record in a calendar year.
The marker was set from the 23rd minute, when Gerard Pique poked home the opener, before Messi and Adriano also struck to send the Blaugrana into a fully deserved three-goal lead at half-time.
Cesc Fabregas added a fourth shortly before the hour mark and despite a consolation effort from Ibai Gomez, Messi scored again with 20 minutes remaining to put the finishing touches on the win.
The hosts fashioned the first clear cut chance of the match, when Andres Iniesta’s agility saw him get the better of Jonas Ramalho and free him for a strike on goal, but Gorka Iraizoz was equal to it and pushed wide.
The Bilbao keeper was left helpless in the 23rd minute however, as he made a brilliant save on a close range effort from Fabregas, only to see Pique dispatch the rebound into the back of the net to give Barca the lead.
And the Catalans doubled that advantage almost immediately after the restart. Messi latched on to a glorious pass from Xavi to clip over Iraizoz, with an attempted clearance by Fernando Amorebieta only serving to accelerate the ball’s progression over the line.
Barca continued to create shooting opportunities, as Pedro and Fabregas both narrowly missed the target, before the latter forced Iraizoz into action again to tip away his low drive towards the corner.
Iniesta then missed badly from a great position inside the box, before Messi thought he had scored after getting past his marker at the near post, but his effort smacked off the underside of the bar.
The third goal would come, however, and it was no surprise to see Messi at the heart of the move. Seemingly surrounded by half the Bilbao team inside the area, the Argentine still managed to pick out Fabregas at the top of the box, who wasted little time in releasing the overlapping Adriano for a confident finish high into the net, right on the stroke of half-time.
The pattern persisted in the second half, as Iraizoz was again called upon to deny Messi, before the Argentine’s control let him down inside the area after a great backheel from Iniesta seemed set to release him.
It was 4-0 in the 57th minute, and Iniesta again was the man setting events in motion, evading his marker at the top of the box before slipping in the unmarked Fabregas for a simple finish from close range.
Bilbao managed to pull one back nine minutes later, with a superb ball over the top from Ander Iturraspe picking out Gomez, whose control afforded him the time he needed to slot between the legs of Victor Valdes.
The respite would not last long, however, as the hosts added a fifth in the 70th minute, with Messi striking again with a right-footed finish into the far corner after a good piece of supportive play from Pedro.
Pique spurned a late chance for a sixth goal as Barca played out the remaining minutes in complete control, and now await the result of the Madrid derby, with the potential for a six-point lead at the top of the table looming should archrivals Real Madrid emerge victorious.