Welcome to Wisteria Lane, home to housewives Susan, Bree, Lynette and Gabrielle (Gaby to all). All seems well until the suicide of friend Mary Alice, who narrates the darkly comedic series from beyond the grave. Despite the tragedy, the housewives cope with jobs, tweak relationships, seek romantic attention…you know, life.
Love’s tangled web flies down the lane. Bree grapples with widowhood as she unwittingly dates the man who killed her husband. Some face big choices: Lynette returns to work and Gaby plans to have a baby.
But all plans have snags. Lynette’s husband welcomes his previously unknown child and her mom, Gaby divorces Carlos and hooks up with the mayor, and Bree’s new husband, Orson, has an odd tie to a dead body. Susan and Edie vie over new neighbor Mike; when he gets amnesia, Edie tries to push Susan aside. Everything changes when a store shooting leaves two neighbors dead.
Eyebrows raise as enigmatic Katherine returns after 12 years. Two new marriages take split paths: Gaby cheats with ex Carlos, and Susan and Mike expect a baby. As Lynette faces cancer, Bree fakes pregnancy to pass off her daughter’s illegitimate child as her own. What’s more, a devastating tornado looms.
Flash forward five years. Susan’s a single mom and Mike’s dating Katherine. Edie’s new hubby Dave plots against Mike, and she dies just after learning his plan. Bree’s career booms, but she’s in a bad marriage and her daughter returns to claim her young son. Gaby struggles with, well, everything.
Katherine loses Mike to Susan, has a breakdown, and decides to experiment with her sexuality. Meanwhile, Susan’s ex Karl and Bree have an affair, and Karl hires a plane with a “marry me” banner. But the plane crashes into a building where Bree, Karl and Orson are, killing Karl. After all, this is Wisteria Lane.
Life stirs up when beautiful Renee moves to the lane, and Gaby and Carlos are shocked by a personal discovery. While Susan copes with money problems and a life-threatening event, a shooting has everyone on edge.
When Carlos kills Gaby’s cruel stepfather, the housewives help in the cover-up. Innocent Bree stands trial for murder, but is acquitted when kind Mrs. McClusky, dying of cancer, confesses to protect her and Carlos. After Mike is shot while protecting Renee, Susan struggles with his death, the cover-up and her daughter’s pregnancy.
Through all the drama, the world's most famous housewives are bound together by the friendship they share…and the secrets they keep.