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Human-related environments, including food and clinical settings, present microorganisms with atypical and challenging conditions that necessitate adaptation. Several cases of novel horizontally acquired genetic material associated with adaptive traits have been recently described, contained within giant transposons named Starships. While a handful of Starships have been identified in domesticated species, their abundance has not yet been systematically explored in human-associated fungi. Here, we investigated whether Starships have shaped the genomes of two major genera of fungi occurring in food and clinical environments, Aspergillus and Penicillium. Using seven independent domestication events, we found in all cases that the domesticated strains or species exhibited significantly greater Starship content compared with close relatives from non-human-related environments. We found a similar pattern in clinical contexts. Our findings have clear implications for agriculture, human health and the food industry as we implicate Starships as a widely recurrent mechanism of gene transfer aiding the rapid adaptation of fungi to novel environments.