In the opening scene, Marlo (Charlize Theron) is brushing her son Jonah's (Asher Miles Fallica) skin, as he has some form of autism and was recommended by doctors to have his skin brushed to make things easier on him. When she is done, Marlo goes to her husband Drew (Ron Livingston) to remind him that they are having dinner the following night at her brother's house, but Drew thinks Marlo's brother hates him.
Marlo, who is nine months pregnant with her third child, takes Jonah and his sister Sarah (Lia Frankland) to school. Jonah throws a tantrum over a specific parking lot before Marlo manages to calm him down. Marlo then goes to meet with the principal, Laurie (Gameela Wright). She tells Marlo that while they like Jonah, his "quirky" behavior is often difficult to deal with and Laurie suggests to Marlo that they hire an aide for the boy.
The family goes to Marlo's brother Craig's (Mark Duplass) home for dinner with his wife Elyse (Elaine Tan), their daughters Greta (Bella Star Choy) and Emmy (Maddie Dixon-Poirier), and their night nanny Shasta (Stormy Ent). Craig and Elyse suggest to Marlo and Drew that they hire a night nanny to help with the baby, as well as their implication that Jonah is too much to deal with. Marlo goes to chat with Craig, who continues to try and sell her on it since he would be paying for the nanny, but Marlo is hesitant.
Marlo's water breaks and she goes to the hospital as the baby arrives. She gives birth to a girl that she names Mia. Upon returning home, Marlo goes through a routine of pumping breast milk, changing diapers, and tending to the baby whenever she cries. She becomes overwhelmed and exhausted.
Marlo brings Mia with her to meet with Laurie again. This time, Laurie suggests that it would be better for everyone if Jonah were "dismissed" from the school and sent to a public school. Marlo gets upset and starts yelling at Laurie, believing she just hates Jonah and thinks he's retarded. She goes back to her car with Mia, who won't stop crying. Fed up, Marlo picks up her phone.
That night, after putting Sarah and Jonah to bed, Marlo is visited by the night nanny, Tully (Mackenzie Davis). She helps Marlo pump breast milk and tend to Mia. The two then chat over Marlo's feelings about being a mother. The following morning, Marlo is surprised to discover that Tully cleaned up the house.
The next night, Tully bakes cupcakes for Jonah's class. Marlo gives one to Laurie to apologize for how she acted toward her.
Jonah later starts his new school with Marlo taking him in on his first day. He has to use the bathroom and he freaks out after flushing the toilet because of how loud it is. Marlo tries to calm him down when a teacher walks by and manages to calm Jonah down by pretending they are trees.
When Marlo sees Tully again, she mentions going through Drew's browser history and seeing that he has some kind of fetish for waitresses wearing a specific uniform from something out of a diner from the 50's. Marlo admits she bought the uniform to wear for Drew, but she never did. Tully goes to put it on, and they go upstairs to wake Drew up and have a threesome with him.
Marlo starts to look and feel better. She goes to a birthday party with Drew, the kids, and Craig and his family, and they note how much more lively she looks.
The next night that Tully comes over, she appears upset over an issue she has with her roommate for bringing so many guys over. She then suggests to Marlo that they go into the city to have some fun. Marlo is initially hesitant but eventually agrees to drive to Brooklyn.
Marlo and Tully drive by Marlo's old neighborhood before going to a bar. They have drinks and jam out to the band that is playing. Tully then tells Marlo that she can no longer work for her because she was only there to bridge a gap and she feels that she is no longer needed. Marlo becomes upset and starts to leave. She steals a bike and rides away with Tully following her on another bike. Marlo tries to go to her old home but then gives up and decides to just drive home. On the way back, Marlo falls asleep at the wheel and swerves off a bridge into the river.
Marlo sees herself trapped underwater in her car. She envisions Tully as a mermaid coming to rescue her.
Marlo wakes up in the hospital where Drew is looking over her. The nurse informs him that Marlo was suffering from sleep deprivation and exhaustion. After Craig arrives, Drew talks to the lady behind the desk to give Marlo's personal information, revealing that her maiden name is Tully. This is when we learn that the Tully that Marlo saw was never real, and that everything she appeared to do with Tully was in her head. Marlo is then visited by "Tully" one last time, where they decide that they have to stop seeing each other, and they part amicably.
Marlo returns home and starts to do better. She goes to brush Jonah's skin, but he decides on his own that he doesn't need it. After hugging him good night, Marlo goes into the kitchen to listen to music and prepare the kids' lunch for the next day. Drew comes in and shares the music with her as he helps her.