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I have conducted some research and to directly answer your questions:
If I change the Automatic forwarding rules setting in Microsoft 365 Defender, does it take precedence over the Remote Domains configuration in Exchange Admin Center?
Technically, neither control strictly "takes precedence" in the traditional sense. When one setting allows external forwarding but another setting blocks it, the block typically wins. They are independent enforcement points, and a block at either layer is sufficient to stop forwarding.
Since forwarding is blocked on the default remote domain and only allowed for selected domains, will setting Defender to Off - Forwarding is disabled block all external auto-forwarding, including those explicitly allowed in Remote Domains?
Yes. If you configure remote domain settings to allow automatic forwarding, but automatic forwarding in the outbound spam filter policy is set to Off, automatically forwarded messages to recipients in the affected domains are blocked. As states in LINK Your Remote Domains allow-list for trusted domains will be overridden.
How do these two controls interact: Exchange Admin Center > Remote Domains and Microsoft 365 Defender > Outbound Anti-spam Policy
In this context, you can think of automatic email forwarding like passing through two separate gates in sequence both must allow it for forwarding to work. The first gate is the anti-spam (Defender) outbound policy, which controls whether a user is allowed to forward messages at all. The second gate is the remote domain setting in Exchange Admin Center (EAC), which controls where those messages can be forwarded. If either one blocks forwarding, the message won’t go through. In practice, this means you can enable forwarding at the policy level but still restrict which external domains users are allowed to send forwarded mail to.
From my perspective view, a useful way to apply this is to allow forwarding in outbound spam filter policies while using remote domains as a more precise allow/block list for specific destinations. Also note that the “Automatic (system-controlled)” setting now behaves the same as “Off,” meaning forwarding is effectively disabled unless you’ve explicitly enabled it in a custom policy.
*You can read here for more information: *Control automatic external email forwarding from cloud mailboxes
Hope my answer will help you.
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