Bryan Mbeumo scored twice in a 3-1 win for Brentford against Southampton at the Gtech Community Stadium.
Former Bees striker Ivan Toney, who signed for Saudi side Al-Ahli on Friday's transfer deadline day, watched on as Mbeumo hit a double to put the hosts in command, while Yoane Wissa added a third.
Mbeumo's first came in the 43rd minute after Taylor Harwood-Bellis lost the ball deep in his own half, allowing Brentford to surge forward.
Kevin Schade's strike hit the post before finding Mbeumo who made no mistake when coolly slotting beyond debutant Aaron Ramsdale.
Cameroon international Mbeumo added his second with a superb finish in the 65th minute after another defensive error from Russell Martin's visitors.
Just four minutes later, the game was put out of reach for Saints as Wissa finished from close range.
Southampton's Yukinari Sugawara brilliantly powered home a consolation five minutes into stoppage time - his team's first goal of their Premier League campaign.
Adam Armstrong had earlier missed a golden opportunity for Saints when his attempt at a volley bounced off his standing leg and fell into the grateful arms of Mark Flekken.
Joe Aribo also went close to scoring for Southampton when the ball deflected off his back and against the Brentford crossbar.
Southampton, without a point after three games, sit 19th in the Premier League while the Bees move up to fifth with this result.
No Toney, no problem
England striker Toney's Brentford departure was confirmed on the eve of this game, with Brentford collecting a fee in the region of £40m.
His natural replacement, Igor Thiago, has been ruled out for several months with a knee injury, so the scoring pressure has fallen on Mbeumo and Wissa.
They stepped up on Saturday to show what they can offer as Brentford look to a future without the prolific Toney.
Once Harwood-Bellis lost possession to present the chance of an opening goal, the duo surged forward with predatory intent.
Mbeumo, alert as ever, was perfectly placed to collect the ball on the rebound before carefully guiding it into the net.
For his second goal, Mbeumo demonstrated composure and finishing ability with a neatly guided effort past Ramsdale.
Wissa added gloss to the scoreline as Brentford brushed off the side that earned promotion through the play-offs.
Is possession-based style hindering Saints?
It is admirable that Martin has insisted on his Southampton side sticking with their possession-based style after earning promotion to the Premier League.
However, much like Vincent Kompany's Burnley last season, Southampton are finding it a struggle to pick up points.
Brentford capitalised on mistakes at the back from Southampton, who will find teams are more clinical in the top flight than rivals were in the Championship.
The Harwood-Bellis error was bad enough.
Then Saints failed to learn from that mistake as Jack Stephens and Jan Bednarek got in each other's way when trying to play out from the back.
Mbeumo, once again, was the beneficiary and he slotted in with a touch of class.
With Southampton yet to get off the mark, Martin has been given food for thought about their style of play as Manchester United await them after the international break.
Player of the match
After the opportunity to rate players has closed, the score displayed represents the average from all the submissions by BBC Sport users.