Sex differences in human navigation and orientation skills are among the most recognized and studied in human cognition. Numerous findings have shown sex biases on various spatial tasks, with males typically outperforming females on popular tasks such as those measuring mental rotation. Other robust sex differences can be found in video game experience and genre preference, where males tend to play more games and prefer to play games with a stronger navigational component compared to females. To date, little is known about how experience playing video games with a specific navigation component affects spatial ability. In this study we explored how sex effects are impacted when controlling for navigation-style video game experience. In a group of 1305 participants, we first analyzed sex effects on a variety of spatial tasks without controlling for video game experience. Following this, we used case-control matching to create groups for each task that did not differ significantly in their age or video game experience. We then used these matched groups to analyze the sex effects for each task while controlling for video game experience. We found that before controlling for video game experience, males significantly outperformed females on our measure of mental rotation ability. However, after accounting for video game experience, there was no significant difference in mental rotation accuracy between females and males. We also found that before controlling for video game experience, there was no significant difference between males and female accuracy on a measure of spatial perspective taking. After controlling for video game experience, we found that females significantly outperformed males in perspective taking accuracy. Our findings suggest that video game experience does change how sex effects in spatial skills are interpreted and should be considered as a relevant confounding variable.