Reducing stigma against people living with HIV is key to encouraging HIV testing, which in turn is an important component in the treatment-as-prevention approach. We analyzed nationally representative survey data of participants aged 15 years and older in Namibia (N = 4,300) to determine whether knowledge about HIV and self-efficacy to protect against sexually transmitted HIV would be independently and jointly associated with stigma against people living with HIV, after controlling for demographics. Findings indicated that having less knowledge and feeling less self-efficacy were associated with greater stigma. Our key interaction hypothesis was also supported: stigma among those with lower self-efficacy to reduce risk of sexually transmitted HIV infection was particularly sensitive to the effects of increased knowledge about HIV. Results highlight the importance of enriching knowledge about HIV transmission modes, prevention strategies, and support services among those with low self-efficacy in order to reduce stigma against people living with HIV, and has useful implications for designing anti-stigma campaigns.