After their plane, Oceanic Air flight 815, tore apart whilst thousands of miles off course, the survivors find themselves on a mysterious deserted island where they soon find out they are not alone.

On March 21, 1963, the inmates and guards at Alcatraz prison mysteriously disappear. To cover up the problem, the government reported the prison has been closed because of unsafe conditions. A secret government unit was set up to find the prisoners. Now, in the present-day, the inmates begin returning - unaged and unaware of where they have spent the missing decades - and continue their criminal ways. They are acting out of character and appear to be searching for specific objects. A federal agent employs a police officer and a conspiracy theory novelist to help track them down.

Steve McGarrett returns home to Oahu, in order to find his father's killer. The governor offers him the chance to run his own task force (Five-0). Steve's team is joined by Chin Ho Kelly, Danny "Danno" Williams, and Kono Kalakaua.