Van der Breggen (Rabo-Liv) launched the decisive attack of the 89km race under driving rain with 6km to go shortly after the start of the 13th and final lap of the Parisian circuit.
Wiggle-Honda’s Jolien D’Hoore finished in second with Amy Pieters (Live-Plantur) rounding out the podium in third.
The 25-year-old’s victory added to an already successful year, which has included the overall title at the Giro Rosa, the most prestigious stage race in the women’s road circuit, and the Belgian classic, La Flèche Wallonne last April.
The Dutch time trial champion succeeded her compatriot and Rabo-Liv team-mate Marianne Vos on the Champs-Élysées. Vos won the inaugural running of La Course in 2014 but has been sidelined for the 2015 season due to injury.
The best placed rider from the Australian Orica-AIS team was Swiss sensation, Emma Johansson in seventh.
It rained hard almost all day long, making the road and cobblestones slippery and putting a damper on the peloton's aggression.
The first breakaway did not come until the seventh lap, when Australian Gracie Elvin went on a solo mission.
The Orica–AIS rider spent just over a lap out front, but she was caught after reaching a maximum buffer of 20 seconds over the front of the peloton. Her team-mate and fellow countrywoman Lizzie Williams seized the chance to attack, but that did not stick either.
Meanwhile, a war of attrition was in full swing in the peloton. Even the slightest sudden touch of the brakes and the shallowest curves turned into danger zones, with riders falling all over the place.
The first mass tumble took place during the second lap and eliminated three riders from the race. Further falls punctuated the race, including one that took down favourite Pauline Ferrand-Prévot (Rabo-Liv) just before the flamme rouge.
Last year's jinx continued for the world champion, Prevot, who saw her hopes dashed by a fall in the same place as last year. The French rider was able to draw some comfort from the fact that it was team-mate van der Breggen who was leading the race.
The Dutch cyclist, who launched out of the bunch with 6km to go, built up a lead of up to 13 seconds, just enough to hold off the charge of a soaked but roaring peloton driven by the sprinters' teams.
It was on the finish line that Anna van der Breggen realised she had it in the bag. She raised her arms at the end of her effort and savoured the prestigious victory, which she gained with one second to spare.