The visitors did not have a shot on target in the first half but took the lead midway through when Mathias Jorgensen’s flick from a corner hit Cesar Azpilicueta on his shoulder to deflect into the back of the net.
The Blues did improve after the break, thanks largely to the introduction of striker Pierre-Emerick Aubameyang, who mis-hit an overhead kick from a dangerous position before firing a low strike at Brentford goalkeeper David Raya.
But they failed to find an equaliser and Brentford wrapped up a hugely impressive win late on when Bryan Mbeumo cut into the box before smashing a shot into the back of the net.
The defeat leaves Chelsea in the bottom half of the table as they sit 11th, six points behind Fulham in 10th and eight behind Brentford, who move up to ninth.