As reported by deusxanime under the Wireguard thread. I am having this exact same issue.
I noticed a possible bug/issue with WireGuard on unRAID. I have a docker container that runs on a custom network and I needed it to talk to a container on bridge so I went into docker settings and enabled "Host access to custom networks". After doing so (and all the required stop/start/reboot), the containers could talk on the network and I thought all was well.
Later that week I tried to use my WG VPN tunnel access (LAN access and tunnel through server to my home internet WAN) on my laptop and phone, which I'd used previously and worked great then, since I was on an untrusted Wifi network. After connecting, I was able to access LAN resources on the unRAID server, but could not get the WG client systems to go out to the internet when I had WG turned on on them. I thought back to what had changed and all I could think of was the setting above. So today, since I had to restart unRAID to add a disk, I disabled that setting to test it out and after restarting I tried WG tunnel access and lo and behold it is working again! I can get to LAN resources as well as out to the WAN/internet while connected to WG on the clients.
So it seems like something with enabling the "Host access to custom networks" setting breaks WG's ability to allow VPN clients to tunnel through it and use the WAN while connected.