Jodi No 1 is the story of two childhood friends, Jai and Veeru, who name themselves after the evergreen characters from Sholay. And being orphans, and having no one else in the world, they swore long ago to follow the same route of friendship. Uneducated, they earn their living by conning people. But both have a bad habit, spending the money that they earn cheating people by gambling in clubs!

While gambling one day, Jai picks a fight with another gambler, Tiger, who was killed. Unfortunately for Jai, Tiger turns out to be younger brother of John, a local Mumbai don. Jai and Veeru are caught by the don's henchmen who take to the don, who in turn wants them killed immediately. Somehow they manage to escape, but the don now has just one overriding ambition in life, to kill them.

While escaping by train from Mumbai to Goa, the duo meet an NRI, Vikramjit, going to meet his uncle, the Raisaab. Jai steals Vikramjit's identity and gets him arrested for travelling ticketless. Jai meanwhile decides they must make their way to the Raisaab's house and take refuge there.

On arriving at the Raisaab's house, they are dazed by the palatial house and factory. Deciding to stay over and clean out his safe and escape, they thank god for what they is their sheer good luck. However they soon get a shock on realising the Raisaab is totally in debt and all his property is mortgaged. Complications arise and Raisaab actually makes them the guardian of his property.

Which puts them in a fix. Faced with the dilemma of protecting the very wealth they had decided to steal, they decide to protect the property. Using a combination of their street smart tactics and roguish charm, they manage to outwit all of Raisaab's opponents.

And just when everything begins to go well, they are shocked to find themselves featuring in an episode of 'India's Most Wanted' with the police on their tracks. And John too arrives chasing them. Escape looks improbable.