My understanding of the history is that the developers of tmux were using screen to develop tmux, because tmux didn't exist yet, so they needed a non-conflicting keystroke.
Obviously they could have switched before a general release, but I guess they had gotten used to it.
Also, many older production machines don't have tmux, so nesting a screen session happens. This is starting to not be a thing, but it was a thing for the trailing 10 years.
Obviously they could have switched before a general release, but I guess they had gotten used to it.