To understand the predominant HIV subtype and drug-resistant viruses in northwest Ethiopia, isolates from 92 antiretroviral drug-naive HIV-1-infected tuberculosis patients were analyzed. Of these patients, 90 (97.8%) were found to be infected with viral subtype C. Other isolates had subtype A (1.1%) and subtype D (1.1%). No primary mutations were associated with protease inhibitor drug resistance. One case (1.1%) had the reverse-transcriptase mutation, V75I. Two patients (2.2%) had the G190A mutation, which confers resistance to the nonnucleoside reverse transcriptase inhibitor, nevirapine. Our study demonstrates that subtype C is the major HIV-1 subtype in northwest Ethiopia. Our results also reveal that the population in the study area had been exposed to antiretrovirals and that treatment-naive patients had drug resistance mutations. Thus, our results emphasize the need for routine drug resistance monitoring in northwest Ethiopia.