Locutus was created when the Borg assimilated Jean-Luc Picard to act as Speaker of the Borg Collective to the Federation, to prepare the people of the Federation for assimilation. Locutus ceased to exist when the link with the Collective was severed and Picard was returned to normal (TNG episode: The Best of Both Worlds). The memory of his time as Locutus would haunt Picard for many years to come (TNG movie: First Contact , et al.)
This Locutus lead the Borg invasion, and in one timeline succeeded in the complete assimilation of the Federation leading the Borg forces to take Earth. However, with the help of the USS Premonition Picard was able to take the USS Enterprise-E back in time to prevent the Borg invasion. Locutus's Cube was destroyed but he managed to escape in a Borg Sphere fleeing back in time to destroy the USS Enterprise-D shortly after its first mission to Farpoint Station. Fortunately the USS Premonition followed Locutus back and destroyed the Sphere before it could attack the Enterprise and alter history. The clone died as a result. (TNG video game: Armada)
In 2380, Picard again heard the "voice" of the Borg and discovered the location of a nearby hive that was close to completing construction on a giant cube and resurrecting the Borg Queen by transforming a normal drone into the appropriate female form.
After losing an Away Team to the Borg, who now attacked on sight, Picard determined that the only way to get close enough to the queen to destroy her was to infiltrate himself, as Locutus.
His transformation was accomplished by Dr. Beverly Crusher, who implanted a chip in Picard's Borg cybernetics that would allow him to remain himself.
The operation didn't go as planned and Picard was captured by the Queen, who finished his transformation back into Locutus. Utilizing a Romulan cloaking device, Commander Worf brought the Enterprise within range of the cube and began a rescue operation.
The Queen was defeated by Dr. Crusher, who had developed a way to reverse the Queen's transformation and revert her to a normal drone. With the Queen's defeat all of her drones, including Locutus, went into hibernation mode.
At some point in the same year, Picard encountered the rogue Vulcan T'Uerell who was attempting to form a Collective of her own in order to impose her cold logic and order on the galaxy. When she encountered Picard's assembled task force of Federation, Klingon Empire and Romulan Star Empire; she refered to Picard as Locutus. (ST video game: Legacy)
Also in the same year, the Borg appeared in orbit of Earth claiming that they had encountered a powerful alien from an alternate universe. They specifically requested the help of Picard. This turned out to be a Borg ruse, however, and the fleet was decimated. But when a version of Data appeared from the future, having been sent by Locutus of 500 years hence, Picard agreed to allow himself to be assimilated again, directly by the queen. He briefly became Locutus again, but in the process introduced a nanovirus to the collective that destroyed them utterly. (TNG comic: "Hive")
- This account contradicts the method of the Borg's destruction seen in Star Trek: Destiny.
In a parallel universe where (among other differences) the USS Enterprise-D's attempt to retrieve Locutus during the intial invasion failed, Locutus managed to circumvent the collective to open rifts to different universes. (TNG comic: "The Worst of Both Worlds")
The Enterprise crew from both universes worked together to retrieve Locutus from the former Starfleet headquarters on Earth and implement an "eat" command, destroying the Borg by forcing them to draw energy all at once. Beverly Crusher then restored the alternate Picard to human form. (TNG comic: "And Death Shall Have No Dominion")
In 2375, Q took Picard to other parallel universes, in order to bring balance to all of reality. They arrived in one where Locutus continued to thrive; deadlier and more consistent than the version of "their" universe. Q was actually relieved when "mon Capitain" finally stopped his pursuit of them, with an explosion. (TNG novel: I, Q)
In an alternate timeline, the Borg succeeded in a ruse to destroy most of Starfleet and, in the process, they re-assimilated Picard. He once again became Locutus, and reigned for 500 years alongside the Borg Queen. He then recreated Data from his stored intelligence and sent him on a mission to the past to destroy the Borg. (TNG comic: "Hive")