Asthma is a heterogeneous condition that is often comorbid with obesity and influenced by diverse risk factors. Elucidating the association of gut microbial characteristics with asthma could improve our understanding of the pathophysiology. Here, we investigate relationships of host genetics and stool microbiota characteristics with asthma among US Hispanic/Latino adults, while considering the influence of obesity status, using host whole genome sequencing and stool shotgun metagenomic microbiota data from participants of the Hispanic Community Health Study/Study of Latinos. We evaluate cross-sectional associations of microbiota characteristics with asthma and analyse whether they are modified by obesity status (body mass index≥30 kg/m). We assess differences in alpha diversity, beta diversity, and taxonomic abundance with asthma, independent of obesity, and interactions between asthma and obesity using covariate-adjusted regression-based methods. We generate an asthma polygenic risk score (PRS) and compare the classification accuracy of genetic and microbial factors for asthma status. We report that asthma is associated with differences in overall taxonomic composition (beta diversity; p = 0.001), which is not dependent on obesity status (p = 0.31). Asthma is not associated with alpha diversity metrics (p > 0.17), though obesity is associated with lower alpha diversity (p  0.01). We identify multiple taxa that are associated with asthma, including decreased abundance of Lactobacillus and Enterococcus species, and some taxonomic associations vary by obesity status. Compared to models including baseline risk factors and an asthma PRS, microbial information improves classification accuracy of asthma (p = 0.04). Our results support that there are microbiota characteristics associated with asthma in Hispanic/Latino adults independent of obesity.