Hey Narutopedia, how y'all doin' today?
As I'm sure we all know by now, nobody's quite sure how the Hashi The Hitta (that's his rap name, check the databook) died. It's simply been said that he died in battle either during or before the First Shinobi World War. Now given the abilities he has (Kage-level, all nature types, Wood Release, Sage, God of Shinobi) and the people (Madara "Hax no Jutsu" Uchiha and Kakuzu/Raggedy Andy) he's defeated, that seems like a big stretch.
What I think happened was that Kishi wrote himself into a corner and just didn't bother to give us a proper answer. If he had maybe succumbed to illness (in this case, Kishimoto AGAIN wrote himself into a corner with that Healing Power/plot device) or his Wood Release, being able to produce life, somehow shortened his own life with repeated use.
...And that does sound like a somewhat decent idea. Yamato and Danzo both experienced exhaustion after repeated/massive Wood Release uses, and as we've seen, using too much chakra can cause death (Kakashi, Nagato). Maybe his Senju longevity is the reason he was able to use it so easily, but that can only do so much. Chakra is spiritual + mental energy, and Hashirama made gigantic dragons and humans and Buddhas on a regular basis. Maybe it just got to the point where his body and mind said "Nope, no more of that. And now you are the dead"...possibly in the middle of a battle.
Or maybe he went out like his brother Tobz and A3; protecting his homies.
Eh, I dunno. Just throwin' that out there. Like Danzo throwing out any credibility he had left by booking it when Sasuke crashed the Kage Summit.