The 44-year-old, already the league's all-time leader in passing yards (81,479), connected with Mike Evans with six seconds left in the first quarter for a nine-yard touchdown to reach the landmark.
He finished the day with four touchdowns in the Bucs dominant 38-3 victory over the Bears, bringing his total touchdown number to 602.
However, instead of letting Brady keep the ball to mark that history-making moment as is typical in the NFL, Evans unwittingly gave it to a lucky nearby fan.
According to CBS' Tracy Wolfson, after some negotiation with the fan, they agreed to swap that ball for another ball and "some kind of signed jersey."
It was Brady's 97th game with three-plus touchdown passes and his 37th game with four or more, both of those marks tied with Drew Brees for tops in NFL history.
For Brady though, it arguably wasn't the moment of the day.
As the game ticked down with the result wrapped up for Brady and the Bucs, he jogged over to the sideline to speak to a young fan who during the match had been holding up a sign which read: "Tom Brady helped me beat brain cancer."
Brady put one of his hats on the young fans' head and shook his hand. The emotion of the moment proved all too much for the fan, who buried his head in his hands as the tears began to flow.
"That was really sweet. Obviously, tough kid, man," Brady said when asked about it in his press conference after the win.
"Puts a lot in perspective with what we're doing on the field; in the end it doesn't mean much compared to what so many go through. We all try to make a difference in different ways and I think so many guys commit times to their foundations and to doing good things for the world.
"And the NFL does a lot of great things, so it's just nice to -- I always think you know do the best that you can do, under any circumstance. It was nice to see."