The trial began on May 24, 2011, at the Orange County Courthouse, with Judge Belvin Perry presiding. In the opening statements, prosecutor Linda Drane Burdick described the story of the disappearance of Caylee Anthony day-by-day. The defense, led by Jose Baez, presented its claim that Caylee drowned accidentally in the family's pool on June 16, 2008, and was found by George Anthony, who then covered up Caylee's death. Baez also alleged that George Anthony had sexually abused Casey since she was 8 years old. Baez also claimed that Casey's brother Lee had made sexual advances toward Casey and was even given a paternity test to see if he was Caylee's father.

The prosecution alleges an intentional murder and is seeking the death penalty against Casey Anthony.