It was entered in 2293 by the USS Excelsior during Captain Sulu's ill-fated rescue of James T. Kirk and Leonard McCoy. There he encountered a Klingon battle cruiser commanded by Captain Kang, who attempted to escort Sulu out of the nebula, but was unfortunately disabled when the Excelsior ignited the nebula's sirillium gas.
The Azure Nebula had a superficial similarity to the class 17 nebula encountered in the Delta Quadrant by the USS Voyager that triggered a memory virus to surface within Lieutenant Tuvok. (VOY: "Flashback")
The Azure Nebula featured heavily in the Star Trek: Destiny trilogy. It was said to be created in 2168, and it contained several subspace passages with exit points all over the Milky Way Galaxy and other galaxies.