Recent research on spatial number representations suggests that the number space is not necessarily horizontally organized and might also be affected by acquired associations between magnitude and sensory experiences in vertical space. Evidence for this claim is, however, controversial. The present study now aims to compare vertical and horizontal spatial associations in mental arithmetic. In Experiment 1, participants solved addition and subtraction problems and indicated the result verbally while moving their outstretched right arm continuously left-, right-, up-, or downwards. The analysis of the problem-solving performances revealed a motion-arithmetic compatibility effect for spatial actions along both the horizontal and the vertical axes. Performances in additions was impaired while making downward compared to upward movements as well as when moving left compared to right and vice versa in subtractions. In Experiment 2, instead of being instructed to perform active body movements, participants calculated while the problems moved in one of the four relative directions on the screen. For visual motions, only the motion-arithmetic compatibility effect for the vertical dimension could be replicated. Taken together, our findings provide first evidence for an impact of spatial processing on mental arithmetic. Moreover, the stronger effect of the vertical dimension supports the idea that mental calculations operate on representations of numerical magnitude that are grounded in a vertically organized mental number space.