Evidence is accumulating that the soil microbiome—the community of microorganisms living in soils—has a major effect on plant traits and fitness. However, most work to date has taken place under controlled laboratory conditions and has not experimentally disentangled the effect of the soil microbiome on plant performance from the effects of key endosymbiotic constituents. As a result, it is difficult to extrapolate from existing data to understand the role of the soil microbiome in natural plant populations. To address this gap, we performed a field experiment using the black medick Medicago lupulina to test how the soil microbiome influences plant performance and colonization by two root endosymbionts (the mutualistic nitrogen-fixing bacteria Ensifer spp. and the parasitic root-knot nematode Meloidogyne hapla) under natural conditions. We inoculated all plants with nitrogen-fixing bacteria and factorially manipulated the soil microbiome and nematode infection. We found that plants grown in microbe-depleted soil exhibit greater mortality, but that among the survivors there was no effect of the soil microbiome on plant performance (shoot biomass, root biomass, or shoot-to-root ratio). The soil microbiome also impacted parasitic nematode infection and affected colonization by mutualistic nitrogen-fixing bacteria in a plant genotype-dependent manner, increasing colonization in some plant genotypes and decreasing it in others. Our results demonstrate the soil microbiome has complex effects on plant-endosymbiont interactions and may be critical for survival under natural conditions.