The 26-year-old was on short-term injured reserve the first seven games of last season with a foot injury, and then he missed the last two weeks with a right knee injury.
He had 38 tackles and returned an interception 71 yards for a touchdown in seven games last year, his fourth with the Falcons after he was drafted in the first round (19th overall) out of Missouri in 2010.
"During Sean's run today with our medical staff, he suffered an injury," Falcons coach Mike Smith said in a statement. "We sent Sean to the doctor for some additional testing and evaluation and unfortunately the results showed that he ruptured his Achilles tendon.
"Sean had been working extremely hard to get back on the field, but regrettably he will miss the entire 2014 season. He will have a procedure done in the near future and we expect him to make a full recovery."
Weatherspoon, who is entering the final year of his contract, has missed 17 games in four seasons. He has 290 tackles in 47 career games.
Falcons LB Sean Weatherspoon ruptured his Achilles today and will miss the 2014 season. — Atlanta_Falcons (@Atlanta_Falcons) June 11, 2014