It should work just fine. Since it supports TTL you shouldn't have to set anything unless you want to.
I think that at best that's an oversimplification. Modern Rebels don't support TTL, AFAIK.
If the speedlite supports E-TTL, set it that way and you should be OK. (But test it before you go on a photo shoot.) If it supports only TTL, you'll probably have to set both the speedlite and the camera to manual flash. If the speedlite has the ability (as many speedlites do) to make its own exposure judgements based on its ISO setting and reading of the ambient light, that may work as well. But the camera will be of no help.
If you use a TTL speedlite on a camera that's using E-TTL, the flash will fire at full power, and the result will be extreme overexposure of the image.
09/26/2023: New firmware updates are available.
08/18/2023: Canon EOS R5 C training series is released.
07/31/2023: New firmware updates are available.
05/31/2023: New firmware updates are available.
05/18/2023: New firmware updates are available.
03/30/2023: New firmware updates are available.