Starfleet Headquarters was the administrative heart of Starfleet Command located adjacent to San Francisco and sharing grounds with Starfleet Academy. Original built by United Earth as the headquarters for Earth's Starfleet after the foundation of the United Federation of Planets it was turned into the HQ for the new Federation Starfleet.
In 2375, Starfleet Headquarters was one of the targets when the Breen attacked Earth. Several building were badly damaged and many people were killed. (DS9: "The Changing Face of Evil"; The Dominion War Sourcebook: The Fires of Armageddon)