On their fifth wedding anniversary, writing teacher Nick Dunne returns home to find his wife Amy missing. Amy's fame as the inspiration for her parents' successful Amazing Amy children's books ensures widespread press coverage. The media find Nick's apathy towards the disappearance suspicious.
Flashbacks in the form of diary entries show a complex reality and a deteriorating marriage. Amazing Amy was an idealized completion of the real Amy's failures. Both Nick and Amy lost their jobs in the recession and moved from New York to Nick's hometown of North Carthage, Missouri, to support his dying mother. Nick grew distant from Amy and began an affair with Andie, one of his students, while Amy became resentful towards Nick for uprooting her.
Detective Rhonda Boney and the forensic team find poorly concealed evidence of struggle and profuse blood loss in the house. Boney learns of financial issues, spousal disputes, and Amy's recent attempt to buy a gun. Medical reports indicate Amy was pregnant, which Nick denies knowledge of.
On every wedding anniversary, Amy had set up elaborate treasure hunts for Nick. This year's clues appear in places where Nick had sex with Andie, thus revealing Amy's knowledge of his affair. Nick discovers thousands of dollars of items purchased with his credit card hidden in his twin sister Margo's woodshed. Amy's clues lead authorities to a half-burnt diary documenting her growing dread of Nick and ending with a genuine fear that he will kill her.
The audience then learns that Amy is alive and hiding in a campground in the Ozarks. After discovering Nick's affair, Amy conceived an elaborate plan to frame him for her murder. She had him ramp up her life insurance and secretly used his credit card to buy the woodshed items. She befriended a pregnant neighbor, told her stories about Nick's temper, and stole her urine to fake a pregnancy, thus eliciting media sympathy after her disappearance. She wrote a diary with increasingly fabricated entries and placed incriminating evidence in the treasure-hunt spots for the police to find. On the morning of her disappearance, Amy drained and splattered her own blood across the kitchen and then cleaned it haphazardly. Her original plan was to drown herself after Nick's arrest and have her body found to ensure his death sentence.
Nick deduces Amy's scheme, convinces Margo of his innocence, and hires lawyer Tanner Bolt, known for representing uxoricide suspects. Nick meets two of Amy's ex-boyfriends: Tommy O'Hara claims he was framed for rape by her after he ended their relationship; wealthy Desi Collings, against whom Amy had filed a restraining order for stalking, turns Nick away.
When Amy's campground neighbors rob her, she calls Desi for help, convincing him that she fled Nick's abuse. Desi agrees to hide her in his lakehouse. Bolt convinces Nick to reveal his affair on a popular talk show, thus seizing the narrative initiative from the media. Andie reveals the affair at a press conference shortly before the show, but Nick insists on conducting the interview. He affirms his innocence and feigns regret for his shortcomings as a spouse, knowing that Amy will be watching.
The interview is a success, garnering widespread sympathy for Nick. However, Boney has already gathered enough murder evidence and arrests Nick and Margo. Bolt bails them out, and they brace for the impending trial. After watching Nick's interview, Amy rekindles her attraction to him and spends weeks crafting her escape story. Using lakehouse surveillance cameras and self-inflicted wrist and vaginal injuries, she makes it appear that Desi kidnapped and raped her. She then seduces Desi, slits his throat during sex, and returns home covered in his blood, thus clearing Nick of suspicion.
Medical examiners lend credence to Amy's story. During questioning, Boney probes her inconsistencies, but Amy spins the focus onto Boney by calling her incompetent. The FBI believes Amy and closes the case, but Boney gleans Amy's guilt. Upon returning home, Amy tells Nick the truth, admitting to Desi's murder. She states that the Nick pleading for her return on TV is the one she wants, and the one who inspired her forgiveness. Nick shares this with Boney, Bolt, and Margo. Despite unanimously agreeing that Amy is guilty, everyone acknowledges a lack of evidence. Bolt wishes Nick well and returns to New York.
A televised interview takes place in their home seven weeks later. Anticipating Nick's intention to leave her and publicly expose her story, Amy reveals her pregnancy minutes before the interview, having inseminated herself with Nick's sperm from a fertility clinic. Nick reacts violently at first but feels responsible for the child and ultimately decides to stay with Amy, despite Margo's despair. The "happy" couple announces on television that they are expecting a child.
