Sensory adaptation serves to adjust awake brains to changing environments on different time scales. However, adaptation has been studied traditionally under anesthesia and for short time periods. Here, we demonstrate in awake rabbits a novel type of sensory adaptation that persists for >1 h and acts on visual thalamocortical neurons and their synapses in the input layers of the visual cortex. Following prolonged visual stimulation (10–30 min), cells in the dorsal lateral geniculate nucleus (LGN) show a severe and prolonged reduction in spontaneous firing rate. This effect is bidirectional, and prolonged visually induced response suppression is followed by a prolonged increase in spontaneous activity. The reduction in thalamic spontaneous activity following prolonged visual activation is accompanied by increases in 1) response reliability, 2) signal detectability, and 3) the ratio of visual signal/spontaneous activity. In addition, following such prolonged activation of an LGN neuron, the monosynaptic currents generated by thalamic impulses in layer 4 of the primary visual cortex are enhanced. These results demonstrate that in awake brains, prolonged sensory stimulation can have a profound, long-lasting effect on the information conveyed by thalamocortical inputs to the visual cortex.