Thanks, that does help. Spack uses both `--with-tcltk-includes` and `--with-tcltk-libs`, and actually RPATHs the libraries in place. According to otool, that is all working fine:

$ otool -L /Users/Adam/spack/opt/spack/darwin-catalina-x86_64/apple-clang-12.0.0/python-3.8.10-fkj5vkn3tpottyv6yqoj5ucz2emstpvo/lib/python3.8/lib-dynload/_tkinter.cpython-38-darwin.so
/Users/Adam/spack/opt/spack/darwin-catalina-x86_64/apple-clang-12.0.0/python-3.8.10-fkj5vkn3tpottyv6yqoj5ucz2emstpvo/lib/python3.8/lib-dynload/_tkinter.cpython-38-darwin.so:
	/Users/Adam/spack/opt/spack/darwin-catalina-x86_64/apple-clang-12.0.0/tcl-8.6.11-n7nea33urrk25rkoqpsc2tdcgai5u4z2/lib/libtcl8.6.dylib (compatibility version 8.6.0, current version 8.6.11)
	/Users/Adam/spack/opt/spack/darwin-catalina-x86_64/apple-clang-12.0.0/tk-8.6.11-ydmhrbboheucxsuhrnyoxqaihgna5dfe/lib/libtk8.6.dylib (compatibility version 8.6.0, current version 8.6.11)
	/usr/lib/libSystem.B.dylib (compatibility version 1.0.0, current version 1281.100.1)

So like you initially thought, the problem isn't that tkinter/_tkinter can't find tcl, it's that tcl can't find tk. I'll talk more with the tcl developers and see how tcl is trying to find tk. Thanks for all of your help!