The 35-year-old former World Cup winning midfielder will play his final game at home against Parma on May 26, but will not be retiring from professional football, AFP reported.
"(De Rossi) plans to pursue a new adventure away from Rome," the club said in a statement.
"It will be the end of an era."
The game could be a crucial one for Roma's Champions League ambitions next season as last year's European semifinalist is sixth in Serie A just one point off fourth place with two games to play.
De Rossi has spent his entire senior career with his hometown team coming through the club's academy system.
"For 18 years, Daniele has been the beating heart of AS Roma's team," said the club president Jim Pallotta.
"We will all shed tears when he pulls on the Giallorossi shirt for the last time against Parma but we respect his desire to prolong his playing career – even if, at almost 36, it will be away from Rome.
"On behalf of everyone at Roma, I’d like to thank Daniele for his incredible dedication to this club and ensure him that our doors will remain open for him to return to the club in a new role whenever he wants.”
Rossi made 615 appearances and scored 63 goals for Roma in all competitions winning the Coppa Italia in 2007 and 2008, and the Supercoppa in 2007.
He took over the captain's armband from club legend Francesco Totti – the one player ahead of him for Roma appearances – in 2017.
He is also the fourth-most capped player for the Italian national team with 117 appearances.
The 2006 World Cup winner retired after Italy failed to qualify for last year's World Cup, missing the tournament for the first time in 60 years.