Gerard Ellis scored two tries, while Johnny Williams and Joe Trayfoot also went over, as the hosts opened up a 24-3 half-time lead.
Alex Lewington crossed twice in the second half, with Rob McCusker and Sean Maitland also scoring within three minutes of each other.
Replacement Felicien Vergnon crossed for Agen's only try after the interval.
London Irish assistant coach Clark Laidlaw told BBC Radio Berkshire:
"We're certainly happier than we have been for the last few weeks. The boys have been working hard for a long time now and it's been a long time between drinks for the club, so we're delighted to get the win.
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"It's a bit better feeling than the last two or three weeks for sure.
"There's large aspects of our game that we need to get better at, but we moved the ball a lot better. We got through a lot more content in our attack and got a bit more flow and rhythm to our game.
"That's what we've worked hard on for the last few weeks, just trying to get that attacking game flowing and a little bit of rhythm."
On playing the game against French opposition the day after the attacks in Paris:
"Sometimes it keeps sport in perspective. We get pretty serious about trying to win games of rugby, but ultimately it's just a sport and we're lucky to work in a game that we all love.
"It gives you that reality that it's just a game. There's a lot bigger things in life than just chasing a rugby ball around a field."
London Irish: Maitland; Lewington, Tikoirotuma, Williams, Ojo; Noakes, Allinson; Court, Ellis, Aulika, Sheriff, Symons (capt), McCusker, Trayfoot, Guest.
Replacements: Cruse, Smallbone, Halavatau, Sisi, Narraway, Murphy, Brophy-Clews, Waldouck.
Agen: Tardieu; Nakosi, Heriteau, Roux, Deschamps; Guemes, Abadie (capt); Bethune, Barthomeuf, Chocou, Roidot, Marchois, Miquel, Gal, Baget.
Replacements: Morlay, Afatia, Ryan, Bastien, Vergnon, Darbo, Bouvier, Sicart.
Referee: Gary Conway (Ireland).
London Irish ran in eight tries in their European Challenge Cup Group Pool 5 victory over French side Agen.