The Runaway Jury follows the case of Celeste Wood, the widow of Jacob Wood, who has died from lung cancer after years of smoking three packs of Bristols a day, versus Pynex, one of the Big Four tobacco companies in the United States.

Although the case has been filed four years ago, we enter the story just weeks before jury selection, when both sides are frantically trying to discover as much about the potential jurors as they possibly can. The tobacco companies have already won many of these cases before, mainly due to a secret account called The Fund. The Fund holds millions of dollars to be spent defending these lawsuits. A man named Rankin Fitch controls The Fund and stops at nothing to get the result that he wants. In contrast to the other cases, the lawyer for the plaintiff, Wendall Rohr, is also well funded and assisted by seven other lawyers.

The jury is selected, and the trial begins in Judge Harkin's court. One day in court, a woman named Marlee hands one of the deputies a note to pass on to Fitch. The note contains information about what the eleventh juror, Nicholas Easter, will be wearing the next day. After following Easter the next day, Fitch discovers that she is right. After a couple of days, Marlee contacts Fitch, again correctly predicting the jury's movements, which begin to get stranger and stranger. She continues to have contact with Fitch, and as time goes on, he learns that she has someone, Easter, on the inside, and Fitch realizes that Easter can control not only the jury's movements, but also the individual jurors' status. Despite appearing to have Marlee on his side, Fitch also buys some insurance by way of bribery and pressure on several of the jurors.

As the trial winds to a close, Marlee makes a deal with Fitch - 10 million dollars for the verdict. She and Easter have proved to this point that they are able to manipulate the people on the jury, even making decisions as to who is actually on it, so Fitch has no reason to doubt her. They make a deal. However, Fitch has not been able to find any concrete information on Marlee's background, despite his constant digging. Finally, some information surfaces - Marlee's parents both died of lung cancer. Fitch receives this information too late.

The jury returns with a decision for the plaintiff to the tune of four hundred two million dollars, a landmark verdict that opens the tobacco companies up for what could be thousands of other lawsuits. Flush with their ten million, Nicholas and Marlee meet up in the Cayman Islands, where Marlee uses the money to buy and trade tobacco shares, taking advantage of the blow that has just hit the industry. She makes an additional eight million dollars, and in a surprise meeting with Fitch, gives the ten million back. For them, the verdict was all that they were looking for.