I think it depends. In my limited experience, because I have not tested this thoroughly, most systems pick the first DNS adresses and only send requests to the second if first doesn't respond.
This has lead at least a couple of times to extremely long timeouts making me think the system is unresponsive, especially with things like kerberos ssh login and such.
I personally set up my DHCP to provide pihole as primary, and my off site IPA master as secondary (so I still have internal split brain DNS working in case the entire VM host goes down).
Now I kinda want to test if that offsite DNS gets any requests in normal use. Maybe would explain some ad leaks on twitch.tv (likely twitch just using the same hosts for video and ads, but who knows).
Edit: If that is indeed the case, I'm not looking forward to maintaining another pihole offsite. Ehhh.