Mike & Molly is a sitcom which premiered in September 2010. The show revolves around the lives of Mike Biggs, a police officer, and Molly Flynn, a schoolteacher, who meet at an Overeaters Anonymous meeting and fall in love. The series follows their relationship with each other and their two families.

Officer Michael "Mike" Biggs, is the lead male protagonist of the series. He is introduced in the first episode as a Chicago police officer with weight issues who attends a meeting of Overeaters Anonymous. It is here that he meets Molly Flynn. After Molly asks Mike to come and speak to her class at the school where she works, they begin dating in the second episode. Mike is regularly accompanied by his best friend, Carl McMillan, his partner on the police force, whom he joins for breakfast to chat about the state of their lives at a cafe where their waiter is always Samuel, an African immigrant who likes to make fun of Mike's weight. Mike and Molly got engaged in the season 1 finale, are married in the season 2 finale, and are still trying to conceive their first child as of the Season 4 premiere. In Season 5, though, Mike finds out that Molly went back on birth control without telling him due to the pain and frustration of two years when she was unable to conceive a child, and they resolve to pursue avenues like adoption as they still love each other and want to raise kids.

Molly Flynn is the lead female protagonist of the series. She is a fourth grade school teacher who attends the same Overeaters Anonymous class as Mike. She lives with her mother Joyce and her sister Victoria, while her mother's partner Vince Moranto is often seen at the house. She is very sweet, intelligent and caring, but she can be hypersensitive and has a very bad financial history thanks to a large amount of credit card debt. She and Mike married in the season 2 finale. She and Mike spent two years trying to have a child but put those plans on hold in Season 5. In Season 4, she quits her teaching job to pursue a career as a writer, and in Season 5 she has a huge success when her literary erotica novel is published by a major company. It is later revealed in a session with a psychologist that Mike's stabilizing presence, something she hasn't had since her father died, has allowed Molly to finally feel comfortable taking risks.

Melissa McCarthy won the Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series in 2011 for her portrayal of Molly Flynn.

Officer Carlton "Carl" Enoch McMillan is Mike Biggs' best friend/surrogate brother and fellow officer on the police force. He lives with his grandma until the middle of Season 3, as he has not been able or motivated to find his own place. Until the middle of Season 2, he did not have a steady girlfriend, and Mike has frequently alluded to Carl employing prostitutes or having one-night stands with strippers. He is quick-witted with a dry sense of humor, and offers droll remarks on various situations. Carl and Samuel become roommates in Season 3, after Carl's grandma kicked him out. After a rather depressing break up with his girlfriend Christina (she leaves him for her ex-husband), he goes through a string of random women until towards the end of season 4, when he begins relationship with Molly's sister Victoria. In an episode before the Season 5 finale, this relationship sours when Carl announces to Mike that he plans to propose to Victoria, only to change his mind. Carl then gets angry with Victoria when she is relieved that he didn't propose, and that leads to a spiral in the Season 5 finale where he has broken up with her. He ends up having a huge fight with Mike when he feels like his best friend is siding with Molly's family over him, and this ultimately leads him to request a transfer so he won't have to work with Mike anymore. Eventually they work out their differences, as both of them hate their new partners and Carl defends Mike when the other cops (including several hard-core macho officers whom they both dislike) make fun of him. In the final episode, it's revealed that he and Victoria were secretly fooling around once again, but in a conversation with Peggy he admits that all of the old feelings were resurfacing, hinting that there's a possibility that they might become a couple again.

Victoria Flynn is Molly's dimwitted but kind, party girl sister who is often high on marijuana. (Policemen Mike and Carl take a "don't tell, we won't ask" attitude about her drug use.) She is employed as a beautician at a funeral home. She likes to have fun and sleeps around, frequently with married men, and her combination of not being particularly bright and being a pothead leads to her often losing or misplacing major items like her car. Harry has an almost obsessive crush on her, and she has on occasion gone on dates with him just to be nice. In Season 3, she starts to realize that Harry is the only man who's ever truly cared for her, and she finally kisses him. In an odd turn of events, he then announces he's gay. As of the end of Season 4, she is in a relationship with Carl, which lasts until the penultimate episode of Season 5 when they have a bitter break up. In the series finale, it's revealed that they're sleeping together, but it is hinted that there is the possibility of it becoming more serious.

Victoria demonstrates a very kind personality consistently through the series. On the night before Mike and Molly's wedding, she has a bonding moment with Molly, telling her that she and Christina worked together and got the church and hall ready despite all the drama that took place at the rehearsal. She also gives Molly a garter to wear which she had made from one of their deceased father's blue silk ties, covering the old, new, borrowed and blue tradition all in one and stating that in a way their father would be walking down the aisle with Molly, which moved both of them to happy tears. After Mike and Peggy got into a fight regarding Mike inviting his father to his wedding, Peggy refused to attend until Victoria talked to her (see below). Peggy changed her mind and told Mike she'd be going, and that it was all right that his father could attend. When Mike wondered aloud what made her change her mind, Victoria never mentions the discussion she had with her, knowing she got through to Peggy. When shown doing her job, she treats the bodies she's tasked to do the makeup on with respect and even wishes one luck on his journey to the other side. In a conversation with Mike while at work, she regretfully reveals what she had to do to make the corpse she was working on smile, which wasn't pleasant. She also reveals that she believes no matter what happens after ones dies they should look their best, demonstrating her kind personality.

Although she is generally dimwitted, high, or drunk (often all at once), Victoria is much more intelligent than other characters give her credit for. When Peggy got into a fight with Mike and announced that she would not attend his wedding because Mike was inviting his father, it was Victoria that convinced her to reconsider by pointing out how well Mike turned out because of Peggy's influence. She also pointed out that she could use the occasion to show Mike's father how well she's done since he left, the mistake he made by leaving, gave suggestions on what she could wear to the wedding to show off her legs (complimenting on how well they've held up) and even offered to help her with her makeup for the day. On that same episode, she has a conversation with Mike about death and what happens after one dies, and even explains her party attitude (she thinks it best to have as good a time as one can while alive in case there's no afterlife). On another occasion Joyce revealed that she's leaving the house to Victoria in her will which irritated Molly (she later explained it to Molly that it wasn't because Victoria was the better choice because she'd take care of the house but because it would force Molly to leave and make a mark on the world, something Joyce was unable to do with her life). A drunk Molly tells Victoria that it was because Molly was Joyce's good daughter and Victoria was a mess. Victoria stood up to Molly, pointing out that she quit her teaching job (which resulted in Molly losing her pension and benefits) and was currently in severe debt due to her wild spending. She then revealed that all of her own credit cards were paid off, has never had nor ever will have any credit card debt and that she could afford a down payment on a house even if Joyce hadn't left her one. She also pointed out that at that moment she was sober and Molly was the mess before going upstairs to see how her stocks performed that day, demonstrating that she had good business sense, something Molly had no idea she possessed.