London Irish were brought down to earth following the high of beating former champions Brive last weekend as Agen ran in four tries on the way to a 28-16 victory.
It was a complete role reversal to the game at The Stoop against Brive, as hooker Jean-Baptiste Rue gathered a try in each half. Irish were on the back foot within six minutes of the start when Octavio Bartolucci crossed for the game's first try.
Former French stand-off Christophe Deylaud added the conversion and he went on to add two penalties.
The boot of Irish full-back Jarrod Cunningham at least kept his side in touch in the first half as his three penalties meant the deficit at the interval was only six points.
The gap was reduced to two points 13 minutes into the second half when lock Nick Harvey burrowed over and Cunnigham added the conversion.
But Brive finished the stronger, and a second try by Rue was followed by another from full-back Cedric Lefranc.