Two physicians caring for the 24-year-old said on Thursday Hamlin was "demonstrating signs of good neurological recovery" and was able to communicate in writing.
He remains on a ventilator in the intensive care unit at University of Cincinnati Medical Center to assist his breathing.
Hamlin collapsed on the field after making a tackle in the first quarter of the game against the Cincinnati Bengals on Monday and had to have his heartbeat restored on the field.
The physicians said Hamlin had asked who won the game between the Bills and the Bengals. The response? "Damar, you won - you won the game of life," Dr Timothy Pritts said.
That his first question was about the outcome of the game showed "it's not only the that lights are on - he's home," one of the doctors said.
Earlier in the day, the Bills said Hamlin had shown "remarkable improvement" over the past 24 hours but remained critically ill.
The next milestone, doctors said, was getting Hamlin breathing completely on his own.
The game, which Cincinnati led 7-3, was later postponed.
The positive update will be welcome news for the Bills, as they prepare for their final regular season contest on Sunday, as well as for sports fans across the United States and around the world who have rallied behind the 24-year-old safety.
Fans, athletes, celebrities and politicians, including US President Joe Biden, have all offered Hamlin their prayers and support.
"Great news," Biden tweeted in response to Hamlin's medical update on Thursday.
"Damar, like I told your mom and dad yesterday, Jill and I - along with all of America - are praying for you and your family."
Famed Niagara Falls - both the American Falls and Canadian Horseshoe Falls - were illuminated in Bills' blue on Tuesday as a show of support for Hamlin, the team and the nearby city of Buffalo.
The NFL has not yet made a decision on whether to complete the Bills-Bengals game.
The postponed game would have playoff implications for both teams, who are battling with the Kansas City Chiefs for the top seed in the American Football Conference.
The Bills are scheduled to host the New England Patriots on Sunday.