What is the most unsettling or disturbing orchestral (or mostly orchestral) piece that you have heard?

Threnody to the Victims of Hiroshima

A warning to those who experience frisson or have high empathy experiences when listening to music - this is uncomfortable. There is a beauty to it, one that is drawn from the very dissonance and frenetic energy in it, but it's a piece that is meant to make you grapple with discomfort.

I had not heard this one before, though I have looked into atonal music one time in the past. This is certainly the most unsettling piece I have ever heard and it is amazing. Thank you for sharing the link.

Let me prefix this by mentioning that I only have minimal experience with the genre.

I think Livre Troisième from Les chants du hasard could qualify as unsettling/disturbing. Also check out their newest album, which goes into a more black metal direction, if you are into that.

The other one that comes to mind is The Umbersun from Elend

I had this discussion with a class the other day. It doesn't answer your question really, but the Requiem for a Dream soundtrack is rather unsettling if you've seen the film.

Can confirm, it's very emotional.

Nick Cave - Tell Me What That Is from the Wind River soundtrack. It’s more sad and unsettling once you know the context and what happens in the film.

So many cool suggestions in the comments, I have to add a mention of Ennio Morrricone's soundtrack to "The Thing".

On a personal note, Shnitke's Concerto Grosso #1 always sounded like a manic bad dream to me.