Butterfly–host plant relationships can inform our understanding of ecological and trophic interactions that contribute to ecosystem function, resiliency, and services. The ecology of danaid–milkweed (Apocynaceae) host plant interactions has been studied in several biomes but is neglected in deserts. Our objective was to determine effects of plant traits, seasonality, and landscape-level host plant availability on selection of Mojave milkweed (Asclepias nyctaginifolia A. Gray) by ovipositing monarch butterflies (Danaus plexippus plexippus) and queen butterflies (Danaus gilippus thersippus) in the Californian Mojave Desert. We surveyed all known Mojave milkweed locations in the Ivanpah Valley, California (n = 419) during early, mid-, and late spring in 2017. For each survey, we counted monarch and queen butterfly eggs on each Mojave milkweed plant. We also measured canopy cover, height, volume, and reproductive stage of each Mojave milkweed plant. We counted a total of 276 queen butterfly eggs and zero monarch butterfly eggs on Mojave milkweed host plants. We determined that count of queen butterfly eggs significantly increased with increasing Mojave milkweed canopy cover. Additionally, count of queen butterfly eggs was: (1) greater on adult Mojave milkweed plants than on juvenile and seedling plants and greater on juvenile Mojave milkweed plants than on seedling plants; and (2) greater during early spring than mid-spring—we recorded no eggs during late spring. Based on aggregation indices, queen butterfly eggs occurred on Mojave milkweed plants in a nonrandom, clustered pattern throughout the Ivanpah Valley. We provide the first evidence of trophic interactions between queen butterflies and Mojave milkweed at multiple spatial scales in the Mojave Desert, suggesting that conservation and management practices for both species should be implemented concurrently. Given its role as an herbivore, pollinator and prey, the queen butterfly may serve as a model organism for understanding effects of anthropogenic disturbance (e.g., solar energy development) on “bottom-up” and trophic interactions among soils, plants and animals in desert ecosystems.