In Harlem, Manhattan Island, N.Y.C, young Annie Bennett (Quvenzhané Wallis) finds herself in a challenging foster care situation with several other girls, all under the supervision of the bitter Colleen Hannigan (Cameron Diaz). Once a successful singer with C+C Music Factory, Colleen has succumbed to a life filled with alcohol and resentment, managing the group of girls with an iron fist, forcing them to complete strenuous chores in anticipation of a city inspector's visit.
Among Annie's fellow foster sisters are Pepper, Isabella, Tessie, and Mia, who all cope with the harsh realities of orphaned life. Despite the difficult circumstances, Annie is bright and imaginative, often turning school assignments into elaborate musical performances. She has a routine of waiting outside Domoni's restaurant every Friday, convinced that her long-lost parents will return for her. This hope is fueled by a note she found on a receipt, which only adds to her determination to discover her past.
An unexpected turn of events occurs when Annie takes a bold step to save a Shiba Inu from bullies, nearly putting herself in harm's way, but is heroically rescued by William Stacks (Jamie Foxx), a germophobic cell phone tycoon running for mayor. This incident goes viral, giving Stacks a significant boost in his campaign as his popularity climbs by five points, just when he most needed it.
Following a suggestion from his campaign manager, Guy Danlily ([Bobby Cannavale]), Stacks invites Annie to lunch, setting in motion a series of events that leads to Annie moving in with him to enhance his public image. As she acclimates to her new environment, Annie flourishes, making friends with Grace Farrell ([Rose Byrne]), Stacks' assistant, and quickly becomes more relatable to the public than Stacks himself.
Their bond deepens as Stacks shares snippets of his own humble beginnings, while Annie helps to connect him with Grace on a more romantic level. During her exciting journey, Annie delights in adopting Sandy, the stray dog she saved, and garners a substantial social media following that eclipses Stacks’.
Their adventures continue when Stacks takes Annie and her foster friends to the premiere of MoonQuake Lake. Although disinterested at first, he finds himself enjoying the film alongside Grace, and they share a playful after-party atmosphere. However, not everything is as it seems at home; at Hannigan's, the foster girls hear their caretaker's bitter musings about wealth and abandonment.
Annie, appreciating the new opportunities she has, attends a charity event where her vulnerability shines through when she admits to struggling with reading. Stacks intends to provide her with the help she needs; however, as his campaign starts to dwindle, Guy plots a scheme with Hannigan—using impostors to falsely claim Annie as their daughter to artificially boost Stacks' popularity.
As the plan unfolds, Annie finds herself kidnapped by these impostors, leading Stacks, Grace, and Colleen into a frantic pursuit, aided by local police. During this intense chase, misunderstandings arise that threaten to fracture the bond formed between Stacks and Annie.
Ultimately, Stacks’ public announcement of his withdrawal from the mayoral race helps clear the air, allowing for heartfelt confessions of love between Stacks and Grace, with Annie caught joyously in the moment. Together, they celebrate Annie’s proclamation of establishing the "Stacks Literacy Centre," dedicated to helping others who, like her, have struggled with literacy.
As the scene crescendos, everyone joins in singing Annie's Tomorrow, with Colleen attempting to prolong her moment in the spotlight despite the awareness of her own doubts and failures. The story encapsulates resilience, hope, and the importance of community in transforming lives.
