On the two-part finale, which will air Sept. 16, Lyonne will play a woman named Tiffani with additional details of her role being kept under wraps.
"Weeds," which casts Tony winner Mary-Louise Parker as a drug-dealing suburban mom, includes stage and screen stars Justin Kirk and Hunter Parrish as well as Elizabeth Perkins and Kevin Nealon, among others. The series was created by Jenji Kohan.
Lyonne, who is best known for playing the role of Jessica in the "American Pie" film franchise, has been seen in the New Group's world premiere of Blood From a Stone and Off-Broadway's Love, Loss, and What I Wore, among others.
"Weeds" airs at 10 PM ET on Showtime. Visit Sho.com/Weeds.