Significance Almost all grain crops grown on commercial farms are hybrid cultivars because these hybrid plants are reliably healthier, larger, and more productive than their inbred parent lines. The widespread and valuable phenomenon of hybrid superiority is called heterosis. Despite over a century of intensive research into heterosis, it is unclear how or why hybrid genomes give rise to superior phenotypes. Most hypotheses and research thus far have focused on genetic and physiological mechanisms of heterosis. In contrast, this article presents evidence for a microbe-driven mechanism of heterosis, whereby the activity of live soil microbes affects the expression of heterosis. This finding will open lines of research that could advance our understanding of heterosis.