Is the button unresponsive in safe mode (hold Option when launching TB)?

Yes, it seems to function correctly in "safe" mode. Does that point to an extension being the culprit?

P.S. I have no extensions installed, however I am using the Mozilla "Light" theme and that may be the culprit. Further testing before I blame it on that...

If extensions aren't a factor, try the default theme in normal mode, then disable hardware acceleration in Preferences/General/Indexing, restart TB. If neither of those help, launch in safe mode, 'Reset toolbars & controls', 'Make changes & restart'.

in macOS, in v68 series TB, i have also noticed some UI related small mis-position, incorrect window position, etc , but in last v68.12.1 those occurred very less.

in newer macOS, because of internal file-system's layout transitions, access-permission, reduction/removal of 32bit support, heavy support for 64bit+, etc, etc, etc changes , various apps exhibited some problems initially when run 1st time , Once installed (or-installed) correctly and access-permissions are allowed/set correctly , then apps can usually perform near normal way.

steps which are pointed-out by user/mod sfhowes in above , solved similar problems for most users , which you can see in this TB support forum.

please make sure you have sufficient free space in your default macOS volume (HDD/SSD).

if you have various types of monitoring/scanning apps, they may conflict (from big or little to none) in some operations , so you may have to adjust them correctly.

More/Related info: • Disable AV/FW/SS software mail-protection OR enable+add+allow EXCEPTIONS in it & add mail-server names/address . Some AV/SS creates insecure proxy/gateway for scanning/checking emails, but there are other secure way to scan/check emails . Please make sure the option "Allow AV to Quarantine email" is selected inside TB, and make sure your AV/SS is set to "Scan all files on access".

sfhowes, I have tried your suggestions regarding enabling the default theme and disabling hardware acceleration in Indexing section, but with no resolution. As far as, "Launch in safe mode, 'Reset toolbars & controls', 'Make changes & restart", I cannot find that option of "reset toolbars & controls".

sfhowes: I have found the solution in the Write (or Reply) window. It is a toolbar setting and I have idea what it's purpose is.... Right-clicking (or control-click) the toolbar showed the "Composition Toolbar" option had a check mark. See first attached image..>

Removing that check restored the Send button to normal function in the "Write" and/or "Reply" windows. See second image..>

Thank you for all suggestions and your help.