After a three-week trial, the jury awarded $329m in total damages, including $129m in compensatory damages and $200m in punitive damages aimed at deterring Tesla from harmful behaviour in the future.
Tesla will be responsible for paying one-third of compensatory damages - $42.5m - and the entirety of the $200m in punitive damages, but according to the company, punitive damages are likely to be capped at a lesser amount.
"Today's verdict is wrong and only works to set back automotive safety and jeopardize Tesla's and the entire industry's efforts to develop and implement life-saving technology," Tesla said in a statement.
Tesla said evidence at the trial showed the driver was solely at fault because he was speeding with his foot on the accelerator, which overrode Autopilot, while looking for his phone and not at the road.
"To be clear, no car in 2019, and none today, would have prevented this crash," Tesla said. "This was never about Autopilot; it was a fiction concocted by plaintiffs' lawyers blaming the car when the driver – from day one – admitted and accepted responsibility."
While there have been other federal lawsuits involving Autopilot during fatal crashes, the Florida case that culminated on Friday was the first federal one to go to a jury.
Last year, Tesla settled a lawsuit over a 2018 crash that killed an Apple engineer after his Model X collided with a highway barrier while operating the company's Autopilot software.
In 2023, a California state jury found Tesla was not at fault in a case in which it was alleged that Autopilot had led to a death.
At trial, Mr McGee said his concept of Tesla's Autopilot was that "it would assist me should I have a failure" or "make a mistake," and that he felt the software had failed him.
Mr McGee has settled a separate lawsuit with the plaintiffs for an undisclosed sum.
Tesla has long faced scrutiny over its Autopilot and self-driving technology, and critics hailed the jury's decision.
"Tesla is finally being held accountable for its defective designs and grossly negligent engineering practices," said Missy Cummings, a robotics professor at George Mason University.
The verdict comes as Tesla is battling weakening sales stemming in part from Mr Musk's political activities.