The 26-year-old Boels-Dolmans rider held off Emma Johnsson (Orica-AIS) and world champion Pauline Ferrand Prevot (Rabo-Liv) in a sprint finish.
Armitstead finished six points clear of Anna van der Breggen (Rabo-Liv), who was sixth in France.
"We did it, a win today and the overall World Cup. Victory is ours," Armitstead tweeted.
Armitstead had won the title for the first time in 2014 with one race to spare, and was intent on not giving up her crown without a fight.
The race came alive with 12km to go when Armitstead reeled in and passed a breakaway group of three riders at the punishing final climb.
The 26-year-old, who claimed Britain's first medal at London 2012 when she won silver in the road race on day two was unable to make a decisive break and was dragged back by four riders, including Van der Breggen.
But Armitstead made a final push for the line holding off a late challenge from Johnsson to claim victory.
Jolien d'Hoore (Wiggle-Honda) had been leading the standings going into the final race but choose to skip it to prepare for the World Championships and slipped to third place.
Briton Lizzie Armitstead retained the UCI Women's Road World Cup in the final round at the GP dePlouay-Bretagne.