Solution 1:

You can use spacebar to toggle mute/unmute.

Credit: http://forum.skype.com/index.php?showtopic=70965&view=findpost&p=2216171

Solution 2:

When Skype is focused, Command+Shift+M toggles the microphone.

Ctrl+Alt+Command+­­ ↑ also mutes the microphone for me, and works globally. However, it's not a toggle; as noted below, it switches to Push To Talk mode, in which the mic is muted by default but will be unmuted as long as Ctrl+Alt+Command+­­ ↑ is pressed.

I'm on OS X 10.8, with the latest version of Skype as of 10/16/2012.

Solution 3:

While the application does not have a built in keyboard shortcut for it you can add one using the Keyboard Shortcuts feature in the Keyboard Preference Pane in System Preferences.

  1. Open System Preferences
  2. Open Keyboard
  3. Change to the Keyboard Shortcuts section (If using Snow Leopard click Application Shortcuts on the left side)
  4. Press the '+' button.
  5. Select Skype as the Application
  6. Menu Title: "Mute"
  7. Choose a Keyboard Shortcut (eg. Command-Option-M as Command-M is used for minimize.)
  8. Press OK, close System Preferences and restart Skype if it was open.