Housewife Julia McNamara's life is already in freefall, dissatisfied with her marriage to plastic surgeon Sean McNamara, and in love with his partner Christian Troy, who she had a one night stand with in college. Due to her unhappiness, Julia flushes her daughter Annie's gerbil down the toilet, and tries to instigate an affair with Christian. Julia returns to college in an effort to finish her doctorate and meets a fellow student named Jude. Julia discovers his attraction to her, and uses it to make Sean jealous. Their friendship ends when Julia discovers that Jude is a professional gigolo who targets middle-aged housewives. Julia drops out of college, and later rallies against her housewife friends when they try and bar MTF transsexual Sofia Lopez from their women's only gym. At the end of the season, Julia decides to get a paternity test done on her son Matt, determined to find an answer that she has been seeking ever since she first slept with Christian in college. Did she conceive Matt during their night together? Julia discovers the results, but decides to keep quiet for now.
Julia's mother, Erica, comes to Miami and proceeds to degrade her and make her feel worthless for not becoming a doctor. Their already fragile relationship is made even worse when Erica sleeps with Christian. Meanwhile, Julia finds she can only orgasm with Sean when thinking about Christian. After Christian loses baby Wilber in the custody battle, Julia reveals to him that he already has a son: Matt. Sean soon discovers the truth as well, pushing Julia against the freezer and throwing her out of the house. Moving into a small apartment which Erica unsurprisingly mocks, Julia self-destructs, gets a boob job and starts to drink heavily. One drinking binge results in an accident where she falls through a glass door. While undergoing surgery to repair her face and remove her implants, Julia is guided through an alternate universe by life coach Ava Moore, where she sees what her life would be like if she married Christian. While she is rich and a successful plastic surgeon, she is also a coke addict, unable to have children, and unfulfilled by Christian. An attempt to seduce Sean also goes awry. Coming out of her dream, Julia realizes that she's never satisfied with what she has, always wondering how life would be on the other side. Despite remaining problems between her and Sean, they reconnect when Julia requires saving after being attacked by a kinky blind date, and later team up in an effort to protect Matt from his potentially dangerous lover, Ava.
Still single, Julia has decided to resort to sleeping with Jude. She also asks Sean for a divorce. In an effort to bring some purpose to her life, Julia teams up with Gina Russo to create and develop De La Mer, a luxury spa. She also poaches Liz from McNamara/Troy, and the three of them create a signature face cream made of semen which they market to Joan Rivers. While running the spa, Julia is romanced by Sean and Christian's new colleague, bisexual doctor Quentin Costa, who goes to work for her. After discovering his affair with a male soldier, Julia dumps and fires him. After a tumultuous argument with her mother, Julia is shocked to discover that the plane Erica was supposed to board has crashed just after take-off. Julia joins Sean and Christian in helping the many injured victims, and finds a horrifically burned woman who she believes is her mother. Putting her out of her misery, Julia suffocates the woman, later confessing to Sean that she feels free. Returning home, Julia is shocked to discover her mother waiting for her, claiming that she delayed her flight due to their argument. Soon after, Julia discovers she is pregnant with Sean's child, the result of a brief sexual encounter earlier in the year. A terrifying nightmare provokes Julia into getting her unborn baby checked for any deformities.
Julia reveals to Sean that their unborn child is suffering from ectrodactyly, a congenital malformation of the hands. The baby, named Conor, is born but the decision on whether he should undergo plastic surgery creates friction between them. Finding herself yet again dissatisfied with her life despite renewing her wedding vows with Sean, Julia starts an affair with Conor's dwarf nanny Marlowe. As she falls deeper in love with Marlowe, she plans to leave for Florence, Italy with him, Annie and Conor. However, Julia eventually decides against this, instead leaving Marlowe to live with her mother in New York City, taking Annie and Connor.
Julia visits Los Angeles and reveals to Sean and Christian that she is currently in a relationship with a woman, Olivia Lord. Olivia encourages Julia to sleep with Christian one last time to "get him out of her system", which she does. After Annie bonds with Olivia's teenage daughter Eden and expresses a desire to go to school with her, Julia permanently moves to the city. Annie and Eden's friendship results in Sean and Julia clashing over Eden's dangerous influence, which results in Annie performing sexual acts on a classmate and worrying about her body image. Julia initially ignores Sean's worry, after Olivia blames Sean's profession for making Annie act out. After a violent encounter with a carjacker, Julia purchases a gun and initiates an affair with Christian. She also threatens Eden after discovering her relationship with Sean. Enraged, Eden begins poisoning Julia with mercury-laced fruitcake. Julia's mystery illness tears apart her affair with Christian, and Julia finally realizes that she wasn't in love with him, but instead in love with a fantasy of him. Olivia returns to Los Angeles, and helps Julia discover that she has mercury poisoning. Julia works out that she had been poisoned through eating the fruitcake and confronts Eden. In desperation Eden uses Julia's gun to shoot her in the head. Julia is rushed to hospital where she is diagnosed with having retrograde amnesia. Visiting her bedside, Sean tells her that he is her husband, and that their family has never been happier.