Nutritional deficiencies affect more than two billion people worldwide, with iron, zinc, vitamin E, and non-provitamin A carotenoids at risk of deficiency in the US. Sweet corn is widely consumed and does not usually provide significant amounts of these compounds. We assessed the natural variability of tocochromanols (vitamin E and antioxidants), carotenoids (provitamin A, lutein, zeaxanthin), and 15 minerals in fresh kernels (~21 DAP) of a sweet corn association panel. For each phenotype, we performed a genome-wide association study to identify the genes involved in the genetic control of their quantitative variation and genomic prediction to provide insights into how best to enhance genetic gains in a sweet corn biofortification program. We identified significant associations of α-tocopherol (highest vitamin E activity) with vte4, as well as content and composition of tocotrienols (antioxidants) with hggt1 and vte1, respectively. We also reported that β-carotene (provitamin A) was associated with crtRB1, and the relative flux between α- and β-branches of the carotenoid pathway was controlled by lcyE. For tocotrienols, we identified associations with two starch biosynthetic genes (su1 and sh2) specific to sweet corn, and reported evidence for the involvement of sh2. Of the 15 studied minerals, iron and zinc were associated with nas5 and cadmium with hma3. Weaker-effect associations specific for a location were observed for calcium (WI) and nickel (NY), and these markers were within ± 250 kb of the genes ras2 and ptr2, respectively. Whole-genome prediction models had moderate prediction abilities for most of the phenotypes measured in the three studies, indicating that these models may be used for developing sweet corn lines with nutrient-dense kernels. Smaller marker datasets that target genes or quantitative trait loci associated with carotenoids or tocochromanols resulted in lower prediction abilities compared to the whole-genome set, but the inclusion of endosperm mutation type in the models increased the abilities for tocotrienols and certain carotenoids. Together, these studies represent the most extensive assessment of natural variation for vitamins and minerals in fresh sweet corn kernels and constitute a key step for improving the nutritional quality of sweet corn for human health.