The plaintiff, cereal farmer Paul Francois, said the decision proved that "David can win against Goliath... And a giant like Monsanto is not above the law."
The case, heard by an appeal court in the southeast city of Lyon, is the first of its kind in France.
The court confirmed a 2012 ruling that Monsanto was "responsible" for the intoxication by its Lasso weedkiller and ordered the US giant to fully compensate Francois.
Monsanto, which has maintained throughout the process that the product was not dangerous, said it would appeal the decision.
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"The decision is very surprising given the inaccuracies and errors that dot Paul Francois's evidence," said the company's lawyer Jean-Daniel Bretzner.
"But this is just another step and the discussion is going to go on and the fight will go on," he added.
Paul Francois argued that Monsanto was aware of the dangers of Lasso long before it was withdrawn from the French market in 2007.