Oropharyngeal upper respiratory tract (URT) infections are a common complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), yet it remains poorly understood how the oropharyngeal URT microbiome contributes to clinical outcomes. In a prospective cohort of 156 recipients, we longitudinally profiled oropharyngeal metagenomes alongside antibiotic exposure and immune profiles. High-risk antibiotics were associated with depletion of endogenous microbes in favor of pathogen dominance, including Enterococcus faecium and Burkholderia cenocepacia. Mediation analysis linked high-risk antibiotic exposure specifically to loss of Prevotella melaninogenica, a modulator of CD8⁺ effector/memory T cells, whose carriage correlated with improved progression-free survival. We identified five reproducible oropharyngeal URT community types, including a newly emerged post-HSCT Burkholderiaceae-enriched cluster that was linked to adverse aGvHD event. A classifier integrating microbial and immune features improved progression prediction in patients with low antibiotic exposure. These findings provide a systematic characterization of the URT microbiome and highlight it as a potential biomarker of HSCT outcomes.