This configuration means Tor Browser will no longer use proxy settings. With no proxy set, Tor Browser uses the (VM) system's default networking. This is identical to any other application inside the Whonix-Workstation ™ that has not been explicitly configured to use Tor via socks proxy settings or a socksifier. This setting is also called transparent torification. 
Note: This action will break both the Stream Isolation for Tor Browser and Tor Browser's tab isolation by socks user name [archive]. This worsens the web fingerprint and causes the user to be pseudonymous, rather than anonymous. To mitigate these risks, consider using More than one Tor Browser in Whonix ™, or better yet, Multiple Whonix-Workstation ™s.
If these settings are changed, expect Tor Button to show a red sign and state "Tor Disabled" if a mouse is hovered over it.
To enable transparent torification (no proxy setting), set the
TOR_TRANSPROXY=1 environment variable. There are several methods, but the #/etc/environment Method is the simplest one.
Note: Choose only 1 method to enable transparent torification.
For other methods with finer granulated settings, please press on Expand on the right.
Command Line Method
Navigate to the Tor Browser folder.
Every time Tor Browser is started, run the following command to set the
TOR_TRANSPROXY=1 environment variable.
This only applies to a single instance of the Tor Browser folder that is configured. This method may not persist when Tor Browser is updated.
Find and open start-tor-browser in the Tor Browser folder in an editor.
This is most likely in ~/tor-browser_en-US/Browser/start-tor-browser below #!/usr/bin/env bash.
This will apply to the whole environment, including any possible custom locations of Tor Browser installation folders. 
/etc/environment in an editor with root rights.
(Qubes-Whonix ™: In TemplateVM)
This box uses
sudoedit for better security [archive]. This is an example and other tools could also achieve the same goal. If this example does not work for you or if you are not using Whonix, please refer to this link.
Add the following line.
Save and reboot.
Reverting this change is undocumented. Simply unsetting that environment variable will not work due to Tor Browser limitations. The easiest way to undo this setting is to install a fresh instance of Tor Browser (please contribute to these instructions)!
Ignore Tor Button's Open Network Settings
Whonix has disabled the
Open Network Settings... menu option in Tor Button. Read the footnote for further information.