In an exciting underworld of illegal dog-fighting in Korea, an FBI agent named John Maxwell, played by Martin Lawrence, becomes the target of a dangerous Korean boss who orders his assassination. Just in the nick of time, John is saved by his undercover partner, the crafty master of disguise, Malcolm Turner. As they find themselves in a precarious situation, a team of FBI agents suddenly bursts into the arena.
Meanwhile, a criminal named Lester Vesco, portrayed by Terrence Howard, manages to orchestrate his escape from prison, where he was serving a life sentence. He kills the attending doctor and steals a car to break free. The FBI quickly assigns Malcolm and John the crucial task of bringing Lester back into custody, sending them to the quaint town of Cartersville, Georgia. They are tasked with surveilling the home of a hefty elderly woman named Hattie Mae Pierce, fondly known as "Big Momma" by her friends. She happens to be the estranged Southern grandmother of Lester's ex-girlfriend, Sherry Pierce, who is played by Nia Long. Sherry is suspected of having assisted Lester during his infamous bank heist by providing him with the vault key.
Unexpectedly, Big Momma leaves town to care for an ill friend, leaving Malcolm and John with the opportunity to enter her house and set up surveillance equipment. The plan takes a twist when a phone call from Sherry prompts Malcolm to impersonate Big Momma, hoping to extract a confession. To prepare for Sherry's arrival the following day, they team up to create a disguise, preparing for the comedic yet risky situation that lies ahead.
When Sherry arrives at Big Momma's residence with her young son, Trent, portrayed by Jascha Washington, Malcolm’s awkwardness in the role leads Sherry to suspect that Big Momma may be losing her faculties. Along the way, Malcolm must navigate the challenges of dealing with Big Momma's overly affectionate boyfriend, Ben Rawley, while also stepping in as an unqualified midwife for Ritha, a woman in labor, and participating in self-defense classes with Ritha's brother, Nolan, played by Anthony Anderson, all of which lead to humorous yet chaotic situations.
After some misadventures, including a near disaster with the disguise, Malcolm finds himself on the porch, pretending to be a handyman when Sherry catches him. Meanwhile, Malcolm builds a rapport with Trent, defending him against bullies and eventually winning a basketball game, while fostering a bond with Sherry through shared experiences like a fishing trip.
Tensions heighten when the group attends a church service where Malcolm, in his Big Momma guise, delivers an uplifting testimony about the value of honesty and transparency. However, as the evening unfolds with a surprise birthday party for Big Momma, the original grandmother surprises everyone by returning early, complicating the FBI's plan. During this chaos, Malcolm discovers the hidden stolen money in Trent's footlocker, leading Sherry to divulge the truth about how she was unknowingly played by Lester.
In a dramatic confrontation, as Lester arrives at the house seeking Sherry and Trent, Malcolm must spring into action. With gunfire erupting and the party thrown into disarray as Malcolm has to fend off Lester, who ultimately learns that his attempts to reclaim his family and fortune are in jeopardy. In a thrilling showdown, Malcolm fights Lester amidst the pandemonium, and despite sustaining injuries himself, he ultimately prevents a tragedy.
As the dust settles, Sherry and Trent are left heartbroken by the revelation that Malcolm was an undercover agent all along. Yet, in a heartwarming conclusion, Malcolm takes the opportunity to express his genuine feelings for both Sherry and Trent during a church service, leading to heartfelt reconciliations, hugs, and a joyful celebration that includes a choir rendition of "Oh Happy Day" as the credits roll.
