Phantasy Star IV takes place 1,000 years after the events of Phantasy Star II. After an event called the Great Collapse, much of the once-thriving planet Motavia has been reduced to desert, and life has become progressively more difficult for the planet's inhabitants. To make matters worse, there has been a marked increase in the numbers of the "biomonsters," a catch-all term for the strange and violent aberrations of Motavia's flora and fauna.

Keeping these creatures under control is the job of "hunters". During an investigation into such an outbreak, Chaz Ashley, a young hunter, learns of the relationship between the biomonster problem and the planet's ecological crisis. The planet is in the process of returning to its original desert state as the climate and biosphere-controlling devices installed over a thousand years previous begin to fail. The reasons behind the malfunctions are clarified as the plot unfolds, relating directly to the events of Phantasy Star II.

Chaz and his allies connect the world's troubles to a cult leader called Zio, "The Black Magician," whose aims appear to be total annihilation, not only of Motavia, but of the whole Algol solar system. The heroes stop Zio in order to restore the computer systems maintaining Motavia. However, it soon becomes clear that Zio is merely the vanguard to a much larger enemy, long buried in the past. The secrets of the Algol star system are revealed as Chaz and company discover both the nature of the threat to their worlds as well as the safeguards placed in a time long forgotten.