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Numerous studies showed a connection between spatial abilities and academic success in different STEM disciplines (see Uttal & Cohen, 2012). We extend previous research by directly comparing this connection across disciplines and including indirect effects. We tested 607 German university freshmen in civil engineering, chemistry and biology with content knowledge tests. Results indicate that, besides prior content knowledge, spatial visualization ability was the strongest predictor of content knowledge, outperforming high-school GPA, mathematical skills, and intelligence. Furthermore, we found substantial indirect effects of spatial visualization ability on content knowledge via prior knowledge and high-school GPA, indicating its relevance starting well before university. These results provide arguments for fostering spatial abilities to facilitate later STEM studies.