Four experiments examined perceptuo-motor associations involved in spatial knowledge encoding and retrieval. Participants learned spatial information by studying a map or by navigating through a real environment and then verified spatial descriptions based on either egocentric or cardinal directional terms. Participants moved the computer mouse to a YES or NO button to verify each statement. We tracked mouse cursor trajectories to examine perceptuo-motor associations in spatial knowledge. An encoding hypothesis predicts that perceptuo-motor associations depend on the involvement of perceptions and actions during encoding, regardless of how spatial knowledge would be used. The retrieval hypothesis predicts that perceptuo-motor associations change as a function of retrieval demands, regardless of how they are learned. The results supported the retrieval hypothesis. Participants showed action compatibility effects with egocentric retrieval, regardless of how spatial information was learned. With well-developed spatial knowledge, a reliable compatibility effect emerged during egocentric retrieval, but no or limited compatibility effects emerged with cardinal retrieval. With less-developed knowledge, the compatibility effects evident during cardinal retrieval suggest a process of egocentric recoding. Other factors of environment learning, such as location proximity and orientation changes, also impacted the compatibility effect, as revealed in the temporal dynamics of mouse movements. Taken together, the results demonstrate that retrieval demands differentially rely upon perceptuo-motor associations in long-term spatial knowledge. This effect is also modulated by environment experience, proximity of learned locations, and experienced orientations.