The Cowboys topped the Giants 37-34 in Week 5, but Sunday's victory was overshadowed by star quarterback Prescott's gruesome ankle injury.
Prescott was in tears as the two-time Pro Bowler left the field on a cart and taken to hospital after he was hurt with just over six minutes remaining in the third quarter while being tackled by Giants defensive back Logan Ryan.
The 27-year-old was consoled by his team-mates and opposition players before raising his right hand in acknowledgment as the two-time Pro Bowler exited the AT&T Stadium field.
Prescott will now have surgery to wash out the wound and fix the fracture, after the injury was splinted with a sterile dressing.
"I feel terrible for him. He was having a tremendous year," head coach Mike McCarthy said. "I have no doubt he will bounce back and this will be another chapter of his great story."
"Losing our leader, losing [number] 4, he means so much to this team," Cowboys running back Ezekiel Elliott said. "It's hard, but we knew we had to go out and do it for him."
Andy Dalton – Prescott's backup quarterback – added: "You absolutely hate it for Dak. The way that he was playing this year and everything he's put into it, I hate to see that for him.
"It's emotional. … It's been a lot of fun to be around him ever since I got here, just to see how he works and how he prepares, and you can see just the way he was playing this year."
There will be doubts over Prescott's future having entered the 2020 season on a one-year exclusive franchise tender after the quarterback and Cowboys were unable to strike a deal on a long-term contract.
Prescott will earn approximately $31.4million for the season before becoming an unrestricted free agent, unless the Cowboys opt to again place the franchise tag on him – a move that would count over $37m towards the 2021 salary cap.
Prescott was drafted by the Cowboys in 2016 and was 14-of-21 for 166 yards against the Giants before the injury.
Since entering the league, Prescott has completed 1,514 of 2,293 passes for 17,634 yards and 106 touchdowns.
Prescott was on pace to set the NFL single-season record for passing yards. In five starts, he had 1,856 yards, nine touchdowns and four interceptions.