So I've had this problem for a while now, it's happened on two different GPUs (a 270x and a rx480) so I know that it isn't hardware related, and I've tried half a dozen driver revisions.
When I navigate to the 'Eyefinity' tab in Radeon Settings, and click on 'quick setup' or 'advanced setup', nothing happens. It won't apply any settings, it won't let me edit any settings, it's just completely unresponsive. It isn't frozen, because I can mouse over the options and they light up. The only way to get it to work is to reboot the computer, at which time the computer boots into Eyefinity mode, as if the changes had been applied and weren't registering, and then changes can be made. It seems to happen after an indeterminate amount of time if the computer is left on for a while.
I do a clean install whenever I update or roll back drivers, and this has happened in every driver revision that's been released this year at least.
Rebooting my computer every time I need to change modes is not convenient for me, I can't deal with it anymore.