This is a minor inconvenience but it is annoying. The issue starts the moment you leave your current game, no matter how you change your preferred layout. It’ll default back to how the game wants you to have it.
Edit: Since it might be possible. someone did mention you need to “Save Custom” keybinds THEN Apply the changes. However, only seems to work for the ONE character you changed it for.
Works fine for me, perhaps you did not save your custom keybinds?
Done exactly that. Doesn’t want to save it.
Weird, it worked fine for me on first try (PC, offline SP). What I did was:
Changed my keybindings
Clicked “Save Custom”
Clicked “Apply”
Maybe you didn’t click apply after you saved it? If you did, then I am out of guesses. 
I’m having the same issue. Whenever I leave the game my custom controls are reset to the default. Hopefully this issue is looked into and resolved in the near future.
That seems to be it. Guess despite “Saving Custom” controls doesn’t mean it is being saved for long term. ~_~
Now just wish they fixed it so it applies to ALL characters being used. That part doesn’t seem to be universal.
I’m having the exact same issues despite saving and applying my custom keybinds. I log off, back in and it’s all reset and I have to start over.
So far this has worked for me on the PC version so far.
Get on one character, and map everything the way you want. Get one character perfect for you.
Click Save Custom.
Click Apply.
Play and test mappings are way you want. After any mapping changes, always hit Save Custom, then Apply.
Get second and any other character into game.
Open Options, Controls.
Click Default button, bottom center.
On the pop-up, click Custom.
Hit Apply, not Save Custom.
Repeat for each character, and have to do this for all new characters as well. It is a pain, but so far this has been working for me instead of manually remapping for each character.
This worked for me in a sense.
Got on main character where keybinds weren’t saving
Map the keys the way I want (don’t waste your time doing everything just yet)
Click Save Custom
Click Apply
Log out to character lobby.
Log into second character and go into game
Open Controls, all keybindings were reset
Map keys the way I want (you can maybe do ALL of them this time if you want)
Click Save Custom
Click Apply
Log out of secondary character
Log back into main character
And finally my key bindings were saved for my main character logging out and in to multiple games to farm.
For me it seems to be any keybinds with Shift modifiers.
I’ve tried all the above, and still when I log out and back it resets any of my Shift binds, but others stay the same
Same issue here.
No matter what actions taken, I cannot save hot keys beyond F1-F8 or other defaults.
Assigning F9-F12 for example, never save whether on a single character, or from one to the next.
Please help @Blizzard
Try under “Gameplay” tab (instead of “Controls”) setting your “Default Key Bindings” to “Custom”.
Megalodon’s thing just worked for me.
Also it is confusing in that when you click “Save Custom” it may not do what you think.
Apparently we have 3 default Key Bindings:
So when you click “Save Custom” it seems to be saving the “Controls” to a file somewhere.
Whereas apply seems to integrate the “Controls” into your current game. Once I figured out this logic it works fine for me. Hence What Megalodon said made sense and fixed it for me so that my saved file 3) “Custom” default keybindings are loaded.
It was a lightbulb moment for me - hope this drawn out explanation helps someone.
Thank youuuuu haha not sure why there is a save AND an apply haha
You son of a… that was it for me as well. I had not been clicking apply after. you would think “save custom” would do just that…
Man i was going crazy trying to save my custom keybinds. Normaly i run through the game settings once or twice and there was no “custom” option when i’ve checked it for the first time (only Legacy and Resurrected). I would never thought, you need to Save Custom, then Apply and only after that go back to Gameplay options, because there you have a new “Custom” settings available.
Now it finaly works. Thank you very much!
Hitting Apply before Save Custom, fixed it for me.