Research activities include imaging and spectroscopy of extragalactic, stellar, solar system and extra-solar bodies, as well as gamma-ray and cosmic-ray astronomy.

Formerly known as the Mount Hopkins Observatory, the observatory was renamed in late 1981 in honor of Fred Lawrence Whipple, a planetary expert, space science pioneer, and director emeritus of SAO, under whose leadership the Arizona facility was established.

The observatory is known for its pioneering work in ground-based gamma-ray astronomy through the development of the Imaging Atmospheric Cherenkov Technique (IACT) with the Whipple 10-meter Telescope during the early 1980s.

In April 2007, VERITAS (a system of 4 IACT telescopes with 12-meter reflectors) started full operations at the FLWO basecamp.

Subsequently, in September 2009, after a 4-month effort, one of the telescopes was moved to a new position, making the array symmetric and increasing its sensitivity.