The primary symbionts of a plant are microbes found in seeds that strongly influence the next generation of both the plant and its microbiome. According to our hypothesis, the primary symbionts of creosote bush (Larrea tridentata, family Zygophyllaceae) should contribute to the prominence of this species in desert plant communities of the American Southwest. In particular, primary symbionts might explain the absence of both conspecific and heterospecific plants in close proximity to creosote bush. In this exploratory investigation, we have isolated bacteria and fungi from seeds of L. tridentata. Over 80% of the microbes isolated were fungal. A representative of each morphotype was sent off for sequencing and screened for pathogenicity against lettuce seed (Lactuca sativa, family Asteraceae). Two bacterial symbionts demonstrated negative effects on emergence when seeds came into direct contact with the microbe prior to sowing. Seedling emergence of heterospecifics (i.e., Achillea millefolium, Lactuca serriola, Bromus tectorum, Layia platyglossa, Lens culinaris, etc.) was further tested with the two bacterial symbionts from L. tridentata seed. One symbiont had either a positive or negative effect on the germination, emergence, growth, and reproductive potential of heterospecific species. In contrast, the other symbiont had either a neutral or negative effect when compared to the control groups. Neither symbiont demonstrated pathogenicity as a foliar application. Additionally, the symbionts had both direct and indirect effects on fungi (e.g., powdery mildew of Lactuca serriola) and competition (e.g., conspecific and heterospecific).