Trying to think of instances where a rules supplement (or a single adventure, maybe) somehow turned into a wholly separate game system eventually. Not necessarily just D&D, though most cases I can think of are of 3rd party D&D supplements.

So far I can think of:
*Arduin, which started out as OD&D houserules
*Arms Law, originally a [3rd party] D&D supplement I think, which turned into Rolemaster.
*Talislanta, which started off as a systemless setting book and later developed its own standalone system.
*Savage Worlds, started out from Deadlands' Great Rail Wars minis skirmish game, although its already got a wholly different system to Deadlands.

Any others ?

The Perrin Conventions.

The recent Ultramodern4 follows Amethyst and the alternative rules designed for Amethyst's alternative setting for D&D4.  

TriStat dX came about from a die choice ruling in Big Eyes Small Mouth.

Of course, D&D came from the alternative rulings built around the fantasy supplement in Chainmail.

Call of Cthulhu, a RQ mod gone mad.
Battletech is in essence a Traveller combat rule writ mech-large. Not a specific supplement to point to, though.

2300 AD was preceded by Sattelite mods in Twilight:2k

Yeah; the "* Law" books for Rolemaster were originally conceived as an alternate combat system for OD&D.

Also, Tekumel started off as essentially OD&D and later became it's own Thing.  With the emphasis on "thing".

Space Marine, not the GW thing but the very much older FGU thing started out as it's own thing and sorta-kinda morphed into ... shoot what was it.  Oh!  Space Opera.

Warhammer Fantasy Role Play became Warhammer Fantasy Role Play 3

In a retrograde maneuver, the very awesome "Solaris VII" boxed set stand-alone game was absorbed by the main line of the Battletech game and a few nods given to it as "play options" in later rules (seriously they should've thrown out the whole system and just used S7...)

I think you could make the argument that Greyhawk became AD&D.

Oh yes: the D&D supplement (satire) "Violence" spawned a follow up booklet that later became Sorceror.

Didn't that embarrassment, the "Book of Erotic Fantasy" go from being a licensed d20 D&D supplement to being it's own OGL thing when Wizards gave them the boot?

Mage the Ascension was a remodel of Ars Magica for a modern setting (to align with the Vampire 1st ED WoD).

Thanks for the input guys. Hadn't known about alot of these. (Though d'oh, should've thought of Chainmail!).
 

Quote from: Philotomy Jurament;548005The Perrin Conventions.

Leading to Runequest? I vaguely recall this being controversial last time this was mentioned, but I forget the details.
 

Quote from: thedungeondelver;548012Didn't that embarrassment, the "Book of Erotic Fantasy" go from being a licensed d20 D&D supplement to being it's own OGL thing when Wizards gave them the boot?

Book of Erotic Fantasy might have changed license types, but I don't believe it ever quite became a full-standalone system. (At least, I hope not).
 
Things do seem to get murkier in the d20 era since things that wouldn've just been supplements of some kind in older eras often got big chunks of the SRD shoved into them - so they started life as complete RPGs but with few new rules.

Hunter: The Reckoning is a sort of descendant of "Hunter's Hunted," much the same occurred with the original Mummy, iirc.

Iron Kingdoms was a d20 setting and supplement for the Warmachine minis game, but is now becomming its own RPG.

Jovian Chronicles began as a setting for Mekton II, then became the default setting for the RPG of the same name.

Delta Green is also becoming its own self-contained game, albeit a supposedly backwards-compatible one.

KoOS

Quote from: jeff37923;548146Iron Kingdoms was a d20 setting and supplement for the Warmachine minis game, but is now becomming its own RPG.

I don't think that's quite right. It was initially a trilogy of 3rd party modules for D&D3.0, out of which eventually sprang Warmachine, Hordes, and the upcoming Iron Kingdoms RPG.

Mercenaries Spies & Private Eyes started life as a T&T article on tunnel delving with modern guns, IIRC.

Quote from: Settembrini;5480092300 AD was preceded by Sattelite mods in Twilight:2k

Um, no. They continued the timeline from Twilight: 2000, but there was never a proto-2300AD in the Twilight: 2000 game anywhere.