Act One, Scene I
Inherit The Wind opens just after dawn on a July day that "promises to be a scorcher." The story centers around a schoolteacher who is on trial for leaching evolution—the theory that man evolved from lower primates such as monkeys—in his classroom, a violation of Tennessee's Butler Law. The lines are already drawn in this sleepy Southern town of Hillsboro, Tennessee. Creationism or evolution? Religion or science? The local minister's daughter, a young teacher named Rachel, visits her imprisoned colleague, Bert Cates, at the local jail. The Baltimore Herald newspaper has sent E. K. Hornbeck, the country's most famous columnist, to cover the trial, along with the nation's most famous trial lawyer, Henry Drummond to defend Bert. The town is abuzz with the impending arrival of the prosecution's lawyer, three-time Presidential candidate and self-proclaimed Bible expert Matthew Harrison Brady. It is clear from the "READ YOUR BIBLE" banner strung across Main Street and the frequent singing of hymns that many of the townspeople are creationists—the religious belief that man was created, fully-evolved, by God—and are against Bert.

Hornbeck, cynical and condescending, supports the merits of Evolution while mocking the views of Creationism. When Brady arrives by special train, the townspeople fawn over him, name him an honorary Colonel in the state militia, and feed him a hearty dinner. Both Brady and the town express surprise and concern when they learn that Henry Drummond will represent the defense. And, when Drummond enters at the end of the scene, he is greeted by Hornbeck with the words, "Hello, Devil. Welcome to Hell."

Act One, Scene II
At the jury selection phase of the trial a few days later, Brady and Tom Davenport, the local District Attorney, trade barbs with Drummond over several potential jurors. The air in the courtroom is more like a circus than a legal proceeding, with numerous spectators and reporters crowding the room. After court adjourns for the day, Rachel begs Bert to stop fighting. Bert wavers, and Drummond agrees to settle the case with Brady if Bert honestly believes he committed a crime "against the citizens of this state and the minds of their children." Bert decides to see things through, leaving Rachel shaken and confused. Drummond is satisfied that he is on the right side.