The Mayer/Delfino family is one of the central families on Desperate Housewives. They reside at 4353 Wisteria Lane (Mike also lived in 4356 Wisteria Lane during seasons 1-3 and 5 and in 4352 Wisteria Lane during season 5). During season 7, they lived in an unidentified apartment complex in Fairview
- Susan Delfino - A known romantic klutz, Susan is the adorable matriarch of the family, whose married two different men, twice each.
- Karl Mayer - Susan's first (and second) husband, Karl cheated on her several times and walked out on their family. They remarried three years later, but redivorced several months later.
- Mike Delfino - Susan's second (third and forth, more so) husband, a plumber with a shady past who moved to the lane to search for his missing girlfriend. Mike and Susan marry at the end of season three, but divorce in between seasons four and five. They remarry season six, but Mike dies in season eight leaving Susan a widow.
- Julie Mayer - Susan's precocious daughter, who would often play the part of the "mother" to her own mother. Julie is Susan's daughter from her first marriage to Karl. Julie has a baby with Porter Scavo in season eight.
- Maynard James "MJ" Delfino - Mike and Susan's young son, who is probably not as bright as his older sister, but cute nonetheless.
- Sophie Mayer-Scavo - The daughter of Julie and Porter, whom the former didn't want at first.
- Sophie Bremmer - Susan's lovable kooky mother, who shares all sorts of characteristics and traits with her daughter, including the klutziness and hopeless romanticism. She has been married five times, these include a drinker, a gambler, a gay, the same gambler, and a pancake store owner who she is currently married to.
- Addison Prudy - Susan's biological father, who owns a supply and feed store, and whose identity was kept in the dark by Sophie for nearly 40 years. He is married to Carol Prudy and has several kids with her.
- Sophie's Ex- Husbands- Three Ex Husband of Sophie before her Marriage with Morty Flickman.1 was a Gambler,2 was Drinker, 3 was a gay and she remarries and redivorces the Drinker
- Morty Flickman - Sophie's forth husband (of her fifth wedding), the owner of a pancake restaurant chain. Before marrying Sophie, he was a widower to a woman named Delores.
- Carol Prudy - Addison's wife of many years, who was cheated on repeatedly. Addison and Carol have a few kids together.
- Susan's Unnamed half siblings - Carol and Addison's unnamed children and Susan's half siblings.
- Claire - Susan's favorite aunt, most likely Sophie's sister (and possibly Tim's mother), who taught Susan how to prepare her favorite drinks at a young age.
- Frank - Susan's gay uncle, who thought no one knew he was gay.
- Ella Bremmer - Susan's aunt. She is possibly the sister of Sophie, Claire, and Regina.
- Regina Bremmer - Susan's rich late aunt who left her a grand piano when she died. She is possibly the sister of Sophie, Claire, and Ella.
- Tim - Susan's younger cousin, whose virginity was taken by Katherine Mayfair when he was 16.
- Adele Delfino - Mike's mother, a typical Southern Belle who criticizes Susan's homemaking skills. She put Mike's older sister, Laura up for adoption because she was autistic and lived to regret it.
- Nick Delfino - Mike's father, who was arrested for homicide, and didn't regret his actions one bit.
- Laura Delfino - Mike's autistic sister, whose existence was kept from him by his mother, and also kept from Susan by Mike himself, until after his passing.
- James Delfino and Maynard - Mike's unseen paternal and maternal grandfathers, respectively. MJ was named after grandpa Maynard, and presumably after Grandpa James as well.
- James Delfino - Mike's cousin named after his paternal grandfather.
- Amy Delfino - Mike's first wife who died a year before the series began. Amy was mentioned three times in season one but not ever again after that. Mike's dog Bongo used to be Amy's until she died.
- Marisa Mayer - Karl's second wife (of his third marriage), a very attractive and younger law professor who left him after six years with their child.
- Evan Mayer - Karl and Marisa's young son, as well as Julie's half brother, a troubled bully who was very affected by his mother's absence. Evan used to bully MJ Delfino but they eventually became good friends.
- Irene Mayer - Karl's favorite aunt who got his piano when he died.
- Gary Grantham - A gay businessman whose mother always wanted to see her son get married to a woman and start a family; he became engaged to Susan when she needed health insurance and he needed a "wife" to please his mother. Gary's life partner however, convinces Gary to not care what his mother says and Gary leaves Susan at the alter.
- Ian Hainsworth - A rich British man whose wife fell into a coma; he became engaged to Susan before leaving her to go back to England so she could be with Mike.
- Jackson Braddock - A painter Susan hired to work on her house, and with whom she developed a romantic relationship; eventually they became engaged to be wed in a fake marriage, in order to trick the feds into letting Jackson stay in the US.
- Bongo - Mike's pet, who belonged to his late wife, and whom he brought with him to the lane.