In the late 24th century, the 5th Fleet was a standing fleet, centered around the Andor sector. With the Andorian homeworld under their watch, the 5th Fleet works closely with the Andorian Defense Force.
Elements of the 5th fleet made up the forces massed at Wolf 359 to battle the Borg in 2367. Along with the 4th and 7th Fleets, the 5th was severely decimated by that confrontation. (Decipher RPG module: Starfleet Operations Manual)
In 2374's Operation Return, the 5th Fleet was teamed with the 2nd Fleet in a victorious effort to retake Deep Space 9. As he assembled his fleets in preparation, Captain Benjamin Sisko caught the notice of Dominion strategists when he withdrew the 5th Fleet away from it's previous position. (DS9 episodes: "Favor the Bold", "Sacrifice of Angels"; DS9 novelization: ...Sacrifice of Angels)
The RPG The Dominion War Sourcebook: The Fires of Armageddon, published by Last Unicorn Games after they had lost their Star Trek licence, states that the fleet was commanded by Admiral Salok and prior to its involvement in Operation Return fought in the First, Second and Third Battles of Vulcanis defended the borders of the Vulcanis system near planet Vulcan, being reinforced by the 13th, 31st and 6th Fleets.