Two goals inside the first half hour gave promotion-chasing Southampton all three points at Griffin Park.
The Saints led 2-0 at the break after dominating the first quarter of the match and sealed it with a late third.
Southampton, who started the day needing seven points from their final three games to ensure promotion, started brightly.
The big-spending outfit were sharper and more incisive, and it was little surprise when they took a 16th minute lead.
They could, and perhaps should, have been ahead long before that.
David Connolly turned a near post cross over the bar inside the first 30 seconds and Guly Do Prado headed over soon after.
Rickie Lambert nodded a Dan Harding cross over soon after before Simon Moore got down well to keep out an Adam Lallana shot, Robbie Neilson cleared the loose ball and when it came back in, Lambert's header was nodded away by Karleigh Osborne.
Eventually Southampton's pressure told - the ball was worked across the pitch to Lallana on the left and he cut inside and drilled the ball past Moore.
It was no less than the visitors deserves, Brentford were a long way second best for the first quarter and although they had delivered some good dead balls, Kelvin Davis had been a virtual spectator.
Brentford hadn't played poorly, they had barely been allowed to play at all.
Jeffrey Schlupp shot wide for The Bees but by the half hour they were two down.
Davis kicked the ball down the middle and it flicked off a couple of heads before Connolly nipped in ahead of Moore to lift the ball in to the net.
The game was a little more even towards the end of the first half - Lambert smashed a free kick wide and Lewis Grabban forced a low save from Davis - but Southampton were largely comfortable.
They continued to have the better chances at the start of the second period - Moore saved at the feet of Connolly after good work by Lallana and then dived full length to deny Richard Chaplow.
Sam Saunders volleyed over for Brentford before Moore saved again, this time from a fierce Lambert free kick.
By the midway point of the half, Brentford had the upper hand and the introduction of Myles Weston gave them an extra spark.
Grabban shot into the side netting after good work on the right and when Marcus Bean couldn't convert a Weston cross and Saunders cut it back, Dean Hammond made a superb tackle to deny Schlupp.
Bean volleyed over soon after before Lambert nodded wide at the other end.
Brentford were handed a way back in to the game when referee Trevor Kettle awarded a penalty when Frazer Richardson brought Weston crashing down.
But Saunders smashed the penalty against the post and Southampton's lead remained intact.
Oscar Gobern had an effort deflected wide but he made no mistake soon after when Danny Butterfield burst in to the box and cut it back for him to finish from eight yards.
Weston blasted one wide late on but Brentford couldn't break through and Southampton took a large step towards The Championship.
Brentford: Moore; O'Connor, Osborne, Neilson, Wood; Reed (sub Weston 63 mins), Bean, Diagouraga, Saunders (sub Byrne 87 mins) Grabban, Schlupp (sub Hacker 75 mins)
Subs (not used): Royce, Spillane, Reeves
Southampton: Davis; Richardson, Fonte, Jaidi, Harding (sub Dickson 72 mins); Do Prado (sub Gobern 31 mins), Hammond, Chaplow, Lallana; Lambert, Connolly (sub Butterfield 85 mins)
Subs (not used): Bialkowski, Forte, Seaborne, Stephens
Booking: Fonte (81 mins)
Attendance: 7,015 (1,820 away fans)
By Chris Wickham