Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.