Background: The number line task assesses the ability to estimate numerical magnitudes. People vary greatly in this ability, and this variability has been previously associated with mathematical skills. However, the sources of individual differences in number line estimation and its association with mathematics are not fully understood. Aims: This large-scale genetically sensitive study uses a twin design to estimate the magnitude of the effects of genes and environments on: (1) individual variation in number line estimation and (2) the covariation of number line estimation with mathematics. Samples: We used over 3,000 8- to 16-year-old twins from the United States, Canada, the United Kingdom, and Russia, and a sample of 1,456 8- to 18-year-old singleton Russian students. Methods: Twins were assessed on: (1) estimation of numerical magnitudes using a number line task and (2) two mathematics components: fluency and problem-solving. Results: Results suggest that environments largely drive individual differences in number line estimation. Both genes and environments contribute to different extents to the number line estimation and mathematics correlation, depending on the sample and mathematics component. Conclusions: Taken together, the results suggest that in more heterogeneous school settings, environments may be more important in driving variation in number line estimation and its association with mathematics, whereas in more homogeneous school settings, genetic effects drive the covariation between number line estimation and mathematics. These results are discussed in the light of development and educational settings.