Okay, really strange error that wasn't happening earlier yesterday...then started happening last night and has not resolved.

I can't use QWER or DF to activate anything in game. All abilities and summoner spells have to be manually activated with a mouse to be used.

So far, I've checked the keybindings in the menu (All good,) restarted computer, repatched my client, and updated my keyboard drivers (just in case.)

Anyone have any ideas? I can still type normally using these keys, so it is not like the keys just don't function. Hoping someone can provide an answer.

I would like for you to try out the following resolution:

1) Create and load into a solo Custom Game, press 'ESC' to open the in-game options
2) Click on the option for "Key Bindings"
3) Change any key binding that is in the list of changeable options and save the changes.
4) Completely exit the game and navigate to the following directory:
C:\Riot Games\League of Legends\RADS\solutions\lol_game_client_sln\release s\[highest version number]\deploy\DATA\CFG
5) Delete the new input.ini file and relaunch League of Legends
6) Once open, the game should repatch and restore a default input.ini file

Just to clarify a bit, I suspect that this issue might be being caused by a failure of the input.ini file. Deleting the file and letting the game re-patch should re-add the file, which may resolve the problem. However, if you're still having trouble with your keybinds (make sure you test it out in a solo custom game!) you should get in touch with one of our technical support specialists by sending us a ticket. When you do, make sure to explain the resolution that I provided:
https://support.leagueoflegends.com/home

Are you using Steam Overlay?
I had this problem more than once when launching League of Legends via Steam (as a non-steam game). Never happened again after I stopped doing it.