Guardfile has one option
which, if set, clears the screen before starting a new run. However, using
guard in a special pane, this satisfies only less because of the history buffer tmux brings.
Add a new shell script in the path, e. g.
#!/bin/bash /usr/bin/clear && [[ -z "$TMUX ]] || tmux clear-history
and make it executable. Now the above mentioned setting will also clear your history buffer for that pane if you're in tmux.