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Antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) have been detected in human-impacted habitats, especially in densely populated cities. The Qinghai–Tibet Plateau is located far from the heavily populated regions of China, and Tibetan residents have distinct dietary habits and gut microbes. Antibiotic-resistance monitoring in the Tibetan population is rare. Here, we collected stool samples from Tibetan outpatients with diarrhea. From 59 samples, 48 antibiotic-resistant Enterobacteriaceae isolates were obtained, including 19 extended-spectrum beta lactamase (ESBL)-producing isolates from 16 patients and 29 polymyxin-resistant isolates from 22 patients. Either ESBL or <i>mcr</i> genes were found in 17 <i>Escherichia coli</i> isolates, approximately 58.8% of which were multidrug-resistant, and ten incompatible plasmid types were found. The gene <i>bla</i>_CTX-M was a common genotype in the ESBL-producing <i>E. coli</i> isolates. Four <i>E. coli</i> isolates contained <i>mcr-1</i>. The same <i>mcr-1</i>-carrying plasmid was found in distinct <i>E. coli</i> isolates obtained from the same sample, thus confirming horizontal transmission of <i>mcr-1</i> between bacteria. Genomic clustering of <i>E. coli</i> isolates obtained from Lhasa, with strains from other regions providing evidence of clone spreading. Our results reveal a strong presence of ARB and ARGs in Tibetan outpatients with diarrhea, implying that ARB and ARGs should be monitored in the Tibetan population.