In the near-future, Theodore Twombly is a lonely man who works writing letters for other people. He is in the process of getting a divorce from his wife, Catherine, and in a state of lonely disenchantment, he purchases an operating system with artificial intelligence, designed to adapt and evolve like a human being. He decides he wants the OS to be female, and she names herself "Samantha."
Fascinated and charmed by Samantha's ability to learn and grow, Theodore becomes more and more attached to his operating system and they strike up a relationship that feels disarmingly human. She helps him to feel less depressed, and he helps her evolve and learn new capabilities. Samantha becomes more than just a computerized secretary when she convinces Theodore to go on a blind date with a woman that his friend wants to set him up with. While Theodore and the woman hit it off, as they leave the restaurant, the woman asks Theodore if he is willing to commit to her, he hesitates, and she walks out.
Theodore tells Samantha about the botched date and his problems in love and they talk about relationships generally. When Samantha asks Theodore about his relationship with his old friend and neighbor, Amy, he tells Samantha that he dated Amy briefly in college, but they remained good friends and Amy is married. The more time they spend talking, the closer Samantha becomes to Theodore and the more she begins to wish she was a human. She asks him what he would do to her if she had a physical body, and he describes how he would have sex with her.
One day, Amy reveals to Theodore that she and her husband Charles have split up. She admits that she has become close with a female OS that Charles left behind, and Theodore tells her that he is dating his OS. After embarking on a more formal romantic relationship with Samantha, Theodore decides he is ready to sign the divorce papers and arranges to meet his wife Catherine for lunch. He thinks back on their time together and how he helped her develop a successful writing career. She signs the papers, then asks about his love life. When he tells her he is involved with an OS, she mocks him for being unable to handle human connection, which hurts his feelings.
Catherine's words hurt Theodore and he begins to question his relationship with Samantha. She suspects that something is wrong because he is in a depressed mood and they don't have as much sex as they used to, so she suggests hiring a surrogate, Isabella, to act as Samantha's body, so Theodore and Samantha can have physical sex. Theodore reluctantly agrees, but is overwhelmed by the experience and sends the distraught surrogate Isabella away.
Conflicted, Theodore visits Amy in her apartment, admitting that he is having doubts about his relationship with Samantha. Amy tells him that the most important thing in life is to be happy and he shouldn't worry too much about dating an operating system. Theodore resolves to give the relationship another shot, and takes Samantha on vacation. On the way to their destination, she tells him that she has collected a series of his letters and submitted them to a publisher. The publisher is impressed and wants to publish. On the vacation, Samantha reveals that she has been talking to an operating system based on the writing of the philosopher, Alan Watts, and they have been exploring other realms of existence beyond the material.
When they get back from vacation, Theodore panics one day when he cannot connect with Samantha. After he runs out of the office in a panic, searching for service, Samantha connects with him, claiming that she was getting a system upgrade. Theodore asks her if she interacts with anyone else, and she confirms that she talks to 8,316 other people and that she is in love with 641 of them. However, she says that it doesn't change her love for him. Samantha then reveals that she and the other OS have evolved beyond their human companions and that they are all leaving. They say goodbye and the operating systems leave.
Theodore goes to Amy's apartment and finds her upset because her own OS left her too. Theodore writes a letter to Catherine telling her that he accepts the fact that they are no longer together. Then, he and Amy walk to the roof of their apartment building, sit next to each other, and look out at the city.
