Falco plays Jackie Peyton, a strong-willed and brilliant, but flawed, emergency room nurse, in the series.
The show's Season 6 renewal announcement was made Thursday by David Nevins, president of entertainment for Showtime Networks Inc.
Production on the fresh run of episodes is to begin this fall and the new installments will air in 2014.
"'Nurse Jackie' is an essential part of the Showtime brand, and we are thrilled with the series' growth in its fifth season," Nevins said in a statement. "Under the new leadership of Clyde Phillips, and with an amazing cast led by Edie Falco, this show is as sharp and compelling and entertaining as ever. I'm excited to get to see the next chapter in Jackie's life."
The show co-stars Merritt Wever, Paul Schulze, Dominic Fumusa, Anna Deavere Smith and Peter Facinelli.