Changing the tmux prefix from Ctrl-b to Ctrl-a moves the command leader closer to the left hand home-row keys and matches the shortcut many GNU Screen users already expect. The change affects every tmux action that starts with the prefix, including opening the command prompt, creating windows, splitting panes, and entering copy mode.
Current tmux still uses Ctrl-b by default and reads its user config from ~/.tmux.conf or an XDG tmux.conf file. The remap itself is a small three-line block: set prefix to C-a, remove the old Ctrl-b binding, and bind Ctrl-a to send-prefix so a second Ctrl-a can still be passed through to the program running inside the pane.
The common failure case is editing the wrong config file or forgetting to reload the running tmux server after saving. When that happens, Ctrl-b still works as the prefix, the new binding is not active, and tmux show-options -gv prefix continues to report C-b.
Related: How to reload the tmux config
Related: How to use copy mode in tmux
$ vi ~/.tmux.conf
Most setups still use ~/.tmux.conf. Current tmux also accepts an XDG config file at $XDG_CONFIG_HOME/tmux/tmux.conf or the default ~/.config/tmux/tmux.conf path, so edit that file instead when the server was started from an XDG path.
set-option -g prefix C-a unbind-key C-b bind-key C-a send-prefix
bind-key C-a send-prefix preserves a literal Ctrl-a for the program inside the pane instead of leaving Ctrl-a as a tmux-only shortcut.
$ tmux source-file ~/.tmux.conf
Use the XDG config path here as well if that is the file the server actually uses.
If tmux returns error connecting to /tmp/tmux-UID/default (No such file or directory), there is no running tmux server to reload yet.
Related: How to reload the tmux config
$ tmux show-options -gv prefix C-a
This confirms that the live tmux server now expects Ctrl-a before normal tmux commands.
Ctrl-a c
Creating a new window proves the attached client is using Ctrl-a as the command prefix.
Ctrl-a Ctrl-a
This forwards Ctrl-a to shells, editors, or other terminal programs that use the key for their own shortcuts.