Main cast

• Andrea Savage as Veronica Von Vandervon: "The Cougar" – A wealthy and classy woman who is known for her vulgar sense of humor and is always on the prowl for younger men. She often insists on explaining her overly suggestive jokes. She speaks in an English accent, although it is later revealed in the reunion that she is in fact not British and only sounds that way because she is white and rich. The sex-obsessed Veronica is an independent businesswoman and the heiress to the "Hot Holes, Heavy Putting" mini-golf fortune.
• Angela Kinsey as Crystal Simmons: "The Religious Zealot" – A devout Christian and local Orlando weather girl. However, she claims to not have actually read the Bible because "it’s written in Jewish." She is known for her "holier than thou" attitude and being judgmental of everyone, especially of her younger sister, Amanda.
• Kristen Schaal as Amanda Simmons: "The Drug Addled Former Child Star" – Crystal's younger sister and a former child star who made her claim-to-fame as the "Florida Prune Juice girl" in a number of commercials as a child. She claims her substance abuse issues are behind her. She is not technically a wife as she is chronically single, but has hopes that being on the show will help her regain her fame.
• Danielle Schneider as Shauna Maducci: "The Bankrupt Overspender" – The brassy Italian-American hotwife with anger control problems. She is addicted to shopping and is constantly fighting with everyone from her husband, Anthony, to her "best friend" Tawny. She and her husband are on the verge of bankruptcy, which she is single-handedly responsible for because of her overspending habits.
• Tymberlee Hill as Phenomenon "Phe Phe" Reed: "The Entrepreneur" – The flashy African-American hotwife known for "speaking her mind", referring to herself in the third person, and coining catchphrases involving her name, such as "I'm just bein' Phe Phe!". Her "entrepreneurial" pursuits include lawyer, foot model, and aspiring taxidermist, among other careers.
• Casey Wilson as Tawny St. John: "The Trophy Wife" – The self-obsessed, gold-digging trophy hotwife who is cheating on her much older husband, Phil, with her fitness trainer, Heath. She defends her actions by claiming that Phil is dying, when he in fact just has allergies. She seemingly has no real marketable skills other than attending charity events, partying, and making music videos, although she has recently attempted to release her own cosmetic products such as her new line of "eyebrow extensions", and also runs a charity called "Classy Canines", which supplies high heels for dogs.

Supporting and recurring cast

• Paul Scheer as Matty Green – The show's executive producer who appears in every episode to plug his after-show, "The Hotwives Cooldown".
• Joey McIntyre as Heath – Tawny's fitness trainer with whom she's having an affair while her husband is on his deathbed.
• Stephen Tobolowsky as Phil – Tawny's much older, wealthy husband, who she thinks is dying, or she hopes is dying anyway. He is completely oblivious to the fact that Tawny is having an affair with Heath.
• Matt Besser as Anthony – Shauna's husband. He and Shauna are constantly fighting and both appear to hate each other.
• Jerry Minor as Rodney – Phe Phe's constantly cheating husband. He works as a sports mascot. He and Phe Phe later get divorced after she catches him in bed with another woman.
• Seth Morris as T.J. – Crystal's very controlling husband, who forbids Crystal from most activities because it goes against the Bible, which she has not read because he claims it is in "Jewish".
• Dannah Phirman as Alli – A wannabe hotwife who is often seen hanging around the ladies, usually trying to spread gossip. She isn't a hotwife but likes to tell everyone she could be.
• Sterling Knight as Billy – Veronica's under-aged boyfriend. He is not very smart.
• Jeff Hiller as Antoine Donner – The party planner often hired by the ladies.

Other guest appearances have included "Weird Al" Yankovic, Kate Walsh, Rich Fulcher, Melissa Rauch, Kulap Vilaysack, Lauren Lapkus, and Horatio Sanz.

Supporting and recurring cast

• Paul Scheer as Matty Green and Vance Silversan – Matty is the show's executive producer who appears in every episode to plug his after-show, "The Hotwives Cooldown". Vance is Ivanka's magician husband who has an oddly close relationship with his sister Callie.
• Keegan-Michael Key as Ace – The fame hungry husband of Jenfer. Was in a relationship with Stephanie but dumped her for Jenfer.
• LaMonica Garrett as Adonis – Phe Phe's con man husband.
• Matt Besser as Kelly – Denise's boyfriend who was a popular impressionist in the '90s known for his 873 voices.
• Jon Gabrus as Junior – Leona's adult son who is entirely dependent on her.

Hotwives of Orlando appearances

• Angela Kinsey as Crystal Simmons – The devout Christian Hotwife of Orlando. She appears during "The Hotwives Cooldown" to discuss Jenfer's pregnancy.
• Jeff Hiller as Antoine Donner – The party planner from Orlando who flies to Las Vegas to plan a party for Ivanka.
• Kristen Schaal as Amanda Simmons – Now 760 days sober, Amanda is supposed to deliver a speech at the AA convention but falls off the wagon when she reconnects with Phe-Phe and unwillingly drinks vodka.
• Danielle Schneider as Shauna Maducci – She appears during "The Hotwives Cooldown", where she immediately starts rambling on violence.

Other guest appearances included "Weird Al" Yankovic, Thomas Lennon, Jackie Siegel, Rob Huebel, June Diane Raphael, Ian Roberts, Dan Bucatinsky, Seth Morris, and Lisa Rinna.