Visual responses are extensively shaped by internal factors. This effect is drastic in the primary visual cortex (V1), where locomotion profoundly increases visually-evoked responses. Here we investigate whether a similar effect exists in another major visual structure, the superior colliculus (SC). By performing 2-photon calcium imaging of head-fixed male and female mice running on a treadmill, we find that only a minority of neurons in the most superficial lamina of the SC display significant changes during locomotion. This modulation includes both increase and decrease in response amplitude and is similar between excitatory and inhibitory neurons. The overall change in the SC is small, whereas V1 responses almost double during locomotion. Additionally, SC neurons display lower response variability and less spontaneous activity than V1 neurons. Together, these experiments indicate that locomotion-dependent modulation is not a widespread phenomenon in the early visual system and that SC and V1 use different strategies to encode visual information.SIGNIFICANCE STATEMENTVisual information captured by the retina is processed in parallel through two major pathways, one reaching the primary visual cortex through the thalamus, and the other projecting to the superior colliculus. The two pathways then merge in the higher areas of the visual cortex. Recent studies have shown that behavioral state such as locomotion is an essential component of vision and can strongly affect visual responses in the thalamocortical pathway. Here we demonstrate that neurons in the mouse superior colliculus and primary visual cortex display striking differences in their modulation by locomotion, as well as in response variability and spontaneous activity. Our results reveal an important "division of labor" in visual processing between these two evolutionarily distinct structures.