The film kicks off with John (Brad Pitt) and Jane Smith (Angelina Jolie) attending marriage counseling, where they are confronted with the grim reality of their relationship. Although they’ve been married for "five or six" years, their intimacy has fizzled to the point that they struggle to recall their last sexual encounter. They reminisce about their first meeting in Bogotá, Colombia, where both were ironically evading the Colombian authorities. Their connection was instant, leading them to fall in love and tie the knot. John recalls how Jane "looked like Christmas morning" when they first met, a memory now overshadowed by their marital discord.
In an unexpected twist, both John and Jane are elite assassins, each affiliated with different organizations and revered as the best in their field. Yet, their styles couldn't be more different: Jane meticulously crafts her schemes, while John adopts a more impulsive, less strategic approach. Each conceals their profession from the other, and as they navigate their seemingly ordinary marriage, the thrill of their secret lives becomes stifling over time.
Their complicated lives take a dramatic turn when they are both assigned the same target, Benjamin "The Tank" Danz (Adam Brody), leading to a chaotic encounter that results in a botched hit. Misunderstanding each other's intentions, they draw the conclusion that they must eliminate one another. After a series of increasingly desperate and confrontational attempts on each other's lives, their conflict erupts into a high-octane showdown in their home. The battle ends with their guns aimed at each other, but ultimately, love prevails as they drop their weapons, choosing to reconnect instead.
However, the reignited partnership of the Smiths quickly faces new threats from their employers, who now see the couple as liabilities to be eliminated. To complicate matters, John's best friend Eddie (Vince Vaughn) refuses a $400,000 bounty for each of them, leaving the Smiths exposed and under siege by a horde of assassins. In a desperate escape, they commandeer their neighbor's minivan and perform a spectacular showdown, eliminating the attackers while squabbling about their very different combat techniques and newfound revelations.
After consulting with Eddie once more, the Smiths resolve to unify against their enemies. They devise a plan to kidnap Danz from his high-security prison, believing this will appease their employers. However, Danz reveals a shocking twist—he was merely bait, ensnared by their work to pit them against each other after discovering their marriage. Notably, Danz wears a Fight Club t-shirt, a nod to John’s (Brad Pitt) past film.
Putting aside their individual strategies, John and Jane prepare for battle as a cohesive unit. In the thrilling climax, they efficiently fend off a vast array of armed forces during an intense shoot-out in a department store, showcasing their newly forged teamwork.
The film concludes with a return to the marriage counselor, where the Smiths express how their relationship has flourished, revealing a deeper love and happiness than ever before.
