It is the third time that the German pharmaceutical group Bayer has been ordered to pay damages over its glyphosate-based herbicide, BBC News reported.
The jury ruled the company had acted negligently, failing to warn of the risks associated with the product.
Bayer denied the allegations. It insisted that Roundup is safe to use.
The company acquired the product last year as part of a $66 billion takeover of US rival Monsanto.
On Monday, a jury in Oakland, California, said Bayer was liable for plaintiffs Alva and Alberta Pilliod contracting non-Hodgkin's lymphoma.
Lawyers for the couple, who are in their 70s, described the damages award as ‘historic’.
"The jury saw for themselves internal company documents demonstrating that, from day one, Monsanto has never had any interest in finding out whether Roundup is safe," said their counsel, Brent Wisner.
The jury awarded each of them $1 billion in punitive damages as well as a total of $55 million in compensatory damages.
In a statement, Bayer said it was disappointed with the verdict and would appeal.
It called the jury's decision ‘excessive and unjustifiable’ adding that both Alva and Alberta Pilliod had histories of illnesses that were known risk factors for non-Hodgkin's lymphoma.
The company insisted that decades of studies have shown glyphosate and Roundup to be safe for human use.
Glyphosate was developed by Monsanto in the US in the 1970s and has become one of the most widely used ingredients in weedkillers worldwide.
But Bayer now faces more than 13,400 US lawsuits over Roundup's alleged cancer risk.
In March, a jury in San Francisco awarded $80 million to another Californian man after finding that Roundup had caused his cancer.
Last August, another Californian man was awarded $289 million after a jury also found Roundup caused his cancer.