High voltage clamps with transient activation and activation release control are provided herein. In certain configurations, an integrated circuit (IC) includes a clamp electrically connected between a first node and a second node and having a control input. The IC further includes a first resistor-capacitor (RC) circuit that activates a detection signal in response to detecting a transient overstress event between the first node and the second node, an active feedback circuit that provides feedback from the first node to the control input of the clamp in response to activation of the detection signal, a second RC circuit that activates a shutdown signal after detecting passage of the transient overstress event based on low pass filtering a voltage difference between the first node and the second node, and a clamp shutdown circuit that turns off the clamp via the control input in response to activation of the shutdown signal.