Brentford took advantage of mistakes made by Southampton and achieved a solid 3-1 victory at home.
In their first match without Ivan Toney, who has transferred to Al-Ahli in Saudi Arabia, Brentford comfortably outperformed Southampton.
Bryan Mbeumo scored twice, and Yoane Wissa added another goal, sealing the fate of the Saints, who have now suffered three consecutive losses since their return to the Premier League.
Under the watchful eye of Toney, who was present in the stands, Brentford demonstrated their strength against Russell Martin's squad.
They created more scoring opportunities and capitalized on a series of mistakes made by Southampton's defense.
Mbeumo scored the first goal just before halftime, then added another midway through the second half, with Wissa finding the net shortly after to further solidify Brentford's promising start to the season.
A late consolation goal from Yukinari Sugawara for Southampton came during injury time.
Currently, Brentford is positioned fifth in the league, while Southampton sits at the bottom with no points.