The jury also found Roundup had been defectively designed, that the company failed to warn of the glyphosate-based herbicide’s cancer risk, and that the company acted negligently.
German chemicals giant Bayer AG, which owns Monsanto, denies the allegations and insists the weedkiller is safe.
The Pilliods were awarded a total of $2bn (£1.5bn) in punitive damages and $55m (£42m) in compensatory damages.
However it is likely the damages award will be reduced because of US Supreme Court rulings that limit the ratio of punitive to compensatory damages to 9:1.
The couple allege the regular use of Roundup on their property between 1975 and 2011 caused them to develop cancers of the lymph system.
They filed their lawsuit in 2017 after Mr Pilliod was diagnosed with cancer in 2011, and Ms Pilliod in 2015.
Both of them are currently in remission, but their trial was expedited because of the risk of a relapse and potentially short life expectancy.
Ms Pilliod called on Bayer to add a warning label to Roundup, saying she and her husband would not have used the product had it alerted them to a cancer risk.
“We’ve been fighting cancer for more than nine years now and we can’t do any of the things we wanted to do,” she said. “We really resent Monsanto for that.”
Bayer now faces more than 13,400 US lawsuits over Roundup’s alleged cancer risk.
Last August, former California school groundskeeper Dewayne Johnson was awarded $289m (£223m) after a jury also found Roundup caused his terminal cancer.
In March, another California man was awarded $80 million (£61.8m) after a jury in San Francisco found the weedkiller caused his cancer. The company said it would appeal both decisions.
Bayer said in a statement on Monday that it was disappointed with the verdict and would appeal.
The company said decades of studies by the company and independent scientists have shown glyphosate and Roundup to be safe for human use.
Bayer also pointed to several regulators around the world that found glyphosate was not carcinogenic to humans.
A spokesman called the jury’s decision “excessive and unjustifiable”.
Associated Press contributed to this report