Steven Masterton's fine free-kick gave Clyde their first win of the season to send Division One rivals Queen of the South crashing out the Challenge Cup.
The winner came in the 13th minute, when Masterton sent a thunderous, curling free-kick high into the net.
Gary Arbuckle sent a header flashing wide as Clyde dominated.
Queens did not threaten until late in the game, when David Bingham sent a shot just wide and a stunning, 25-yard Stevie Tosh drive struck the bar.
Clyde: Hutton, McGregor, Potter, Higgins, Smith (Dougherty 75), Masterton, Bradley, MacLennan (Wilson 75), Arbuckle, Imrie, David McGowan.
Subs Not Used: McKenna, Traub, Cherry.
Goal: Masterton 13.
Queen of the South: Grindlay, Paton, McQuilken, MacFarlane, Lauchlan, McGowan (Aitken 79), O'Neill, Tosh, O'Connor, Dobbie (Jamie Mole 79), Gilmour (Bingham 46).
Subs Not Used: Scally, MacDonald.
Ref: J Underhill