John, a construction executive, and Jane, a tech support consultant, are answering questions during marriage counselling. The couple has been married for five or six years, but their marriage is on the rocks. They talk about how they first met in Bogotá, Colombia, claiming to be together to avoid being questioned by Colombian authorities; the two fell in love and got married.
In reality, John and Jane are both skilled field operatives and work for separate contract-killing firms; they are both among the best in their field and adept at concealing their true profession from the other.
The Smiths live in a large Colonial Revival house in the New York suburbs keeping up appearances by reluctantly socializing with their "conventionally" wealthy neighbors. Underneath their cover stories, John and Jane balance their marriage, which is apparently mundane—after a few years, both agree it is becoming dull and suffocating—with their secretive careers. After they are both assigned to kill DIA prisoner Benjamin "the Tank" Danz in a prison transfer, they run into each other on the job and the hit is botched.
Danz survives; John and Jane are assigned to kill each other instead. After attempts on each other's lives escalate, the Smiths' conflict ends in a massive shootout which nearly demolishes their home. During a protracted, evenly-matched fight, they pull guns aiming at each other's heads. John declines to shoot saying that he loves Jane and lays his gun down. Jane discovers that she cannot shoot John either and they spend a passionate night together. The renewed Smith partnership is quickly threatened by their employers who join forces to eliminate the couple.
Eddie, John's best friend and co-worker, turns down a bounty of $400,000 for each of them. The Smiths find themselves under attack from an army of assassins. Their pockmarked house is blown up, and the Smiths steal their neighbour's minivan and are able to destroy their attackers' pursuing armoured sedans while they bicker about their fighting styles and personal secrets they have discovered about each other. They meet with Eddie and decide to save their marriage.
The Smiths kidnap Danz from his high-security prison to use as a bargaining chip. He tells them that he is merely bait and an intern hired by each of their employers after they discovered the Smiths were married; his clients hoped the Smiths would kill each other. Discarding each of their contingency plans the two make a last stand together, fending off an assault inside a home decorating store by heavily armed operatives. The film ends with the couple meeting their marriage counselor again; the Smiths say their marriage is thriving.
