Rose Cooper is an uptight and by-the-book cop whose name has become a verb synonymous with screw-ups, and she’s found a chance to redeem herself. She has been assigned to protect a federal witness, Daniella Riva, the vivacious and outgoing widow of a drug boss. As the two polar opposites race through Texas, they find themselves pursues by everyone from crooked cops to murderous gunmen. However, their greatest obstacle to making this out alive may be themselves as they learn that Cooper has now been considered a fugitive fleeing with Danielle.
Practically since she was a baby, Rose Cooper (Reese Witherspoon) has always tagged along with her father, a respected police officer in San Antonio, Texas, in his police cruiser. As she got older, he let her ride along for some of his arrests. This inspired Cooper to pursue a career in law enforcement. However, as an adult, her drive for her work has made her too intense in her personal life. While out on a date, she scares the guy away after she defensively pulls a gun on him. She chases him down just to give him back his wallet.At the station, Cooper is brought in to meet Detective Jackson (Richard T. Jones). Captain Emmett (John Carroll Lynch) informs Cooper that he will escort Jackson to protect a cartel informant named Felipe Riva (Vincent Laresca) and his wife Daniella (Sofia Vergara) after Felipe decides to testify against notorious cartel leader Vicente Cortez (Joaquin Cosio) up in Dallas. This is Cooper's first job back in the field after her last incident where a few months earlier she saw the mayor's son yell "Shotgun!" while out with his friends, leading Cooper to tase him in a spot where he spilled alcohol and causing him to catch fire. Cooper's name has become a verb synonymous with screw-ups, and she's found a chance to redeem himself.Cooper and Jackson arrive at the Riva home, where Daniella is pissed at her husband for making them targets. Cooper finds her packing a bunch of materials with her. Downstairs, gunshots start to ring out. Two masked men shoot at Jackson and Felipe. The two of them are shot and killed. Cooper runs to the garage to find Daniella hiding in the backseat of a car. Cooper turns the car on and drives away from the scene. She breaks the news of Felipe's death to Daniella, making her wail hysterically. She tries to call for help, but Cooper makes her drop the phone on the road. Cooper pulls the car over, and Daniella grabs her bag to walk away on her own. Cooper handcuffs herself to Daniella to make sure she's close to her. Then a truck plows into the car, spraying a ton of hidden cocaine everywhere. Cooper gets jacked up on coke and gets the truck driver to drive them to a nearby store to get new clothes.The ladies learn that Cooper is now considered a fugitive that has taken Daniella with her. Cooper phones someone at the station to identify the shooters. She notes that one had a longhorn tattoo. The ladies are found by Cooper's fellow officers Dixon (Michael Mosley) and Hauser (Matthew Del Negro). Unfortunately, they're recognized as the shooters since Hauser has the longhorn tattoo. The ladies pretend that Daniella is having her period so they can go to the bathroom and make their escape. They try to sneak out a window, but Dixon is standing watch. Cooper fires her gun to alert them, and giving them a chance to get away. They stow away in the back of a wagon hooked to a truck. There, Cooper inquires about what's in Daniella's luggage. It's a bunch of pairs of shoes that have diamonds on them. Daniella claims they were given to her by her brother before his passing, and it's the only thing she has to remember him by.Cooper tries to get into the truck, until the owner, Red (Jim Gaffigan), comes out with a gun. Daniella tries to make her escape, but comes back for Cooper and defends her by pretending to be her lesbian lover. She starts to uncomfortably grope and make out with Cooper, briefly seducing Red until he accidentally shoots off his finger. Cooper and Daniella then grab another truck and drive away.On the road, the ladies bond a little more, with Cooper admitting that her by-the-books nature has made it difficult for her to find a man. There already happens to be a man sleeping in the back of the truck. The ladies pull over again and find out that the man, Randy (Robert Kazinsky), is a felon with an ankle bracelet put on after he beat the crap out of his sisters' abusive boyfriends. They reach an agreement for Randy to help the ladies if they take off the bracelet. Cooper gets it off, and Randy appears to flirt with her, to Daniella's joy.The three stop at a hotel room for the night. Cooper cuffs Daniella to the bedpost while she goes to Randy's room to get food. She walks in on him naked and eventually succumbs to his charms and kisses him. He goes to get her some food. Cooper goes back to her room to find Daniella aiming Cooper's gun at her. She found Cooper's little notebook which suggests that Daniella wouldn't be smart enough to properly testify. Cooper then learns that the shoes in Daniella's luggage are worth $4 million and that this is how Felipe laundered money. Dixon and Hauser then show up at the door and try to shoot at the ladies as they make their escape. Randy finds Hauser pointing his gun at the ladies, and he starts beating the crap out of him, allowing them to run.The ladies make their escape on a tour bus. The crooked cops chase after them while two of Cortez's thugs follow closely. One of the thugs shoots out the tires of the villains' car, and the ladies manage to bump them off the road. The bus stops, and Daniella punches Cooper's lights out.When she comes to, Cooper sees Daniella walking away with the thugs. She learns that Daniella is working with them as part of her plan to murder Cortez as payback for him killing Daniella's brother. Knowing that he will be free and attending his granddaughter's quinceañera, she plans to get him there. Daniella also arranged for the thugs to kidnap her but did not plan for her husband to die. She cuffs Cooper to a pole and leaves.Back at the police station in San Antonio, Cooper is commended by Emmett for bringing in Dixon and Hauser despite failing the rest of the mission. He tells her to go home, but she knows her mission isn't over.Cooper travels to Dallas and sneaks into the quinceañera as a man to get close to Daniella. She tries to get her to wear a wire so that they can get Cortez to confess to her brother's murder, but a woman walking into the bathroom mistakes Cooper for a pervert and throws her out. She gets back in dressed as a server of the place, running into Emmett and learning he is a bad guy. He tries to make her walk through the kitchen with his gun on her, but Cooper turns the tables by pouring alcohol on him and tasing him so he catches fire. She puts out the flames and knocks him out with a fire extinguisher.Daniella gets Cortez alone in a room and reveals her intentions to kill him. He came prepared with his own gun. Cooper arrives and stops anything from happening. She ties Cortez's hands together and convinces Daniella not to kill him. She sees Cortez drawing his gun, and Cooper shoots him dead. Daniella is pissed at Cooper for denying her the satisfaction of killing Cortez herself until she sees that Cooper took a bullet for her in the arm.Three months later, Cooper goes to pick Daniella up from prison after she serves her time for obstruction of justice. Cooper is no longer a laughingstock and is praised for taking down Cortez. Outside, she presents Daniella with her shoes. They leave together, and Daniella sees that Cooper brought Randy along with her.During the end credits, several bloopers and outtakes from the film are shown.