Although HIV prevalence in Uganda is much lower than it once was, AIDS is still claiming many lives each year with clear signs of escalating rural epidemics. The objective of this study was to appraise the socio-economic and demographic dynamics of HIV/AIDS epidemic in South-Western Uganda. Data were collected with standard closed ended semi-structured questionnaires self-administered to consenting, 605 HIV/AIDS patients, selected using the multistage random sampling technique, logistic linear regression, randomized block design and Pearson's Chi square test (α=0.01) were used to analyse the data obtained. The duration of carriage was inversely proportional (r=-0.94) to population of HIV/AIDS patients surveyed. There were 98.2% Bantu (55.5% Banyankole and 22.6% Baganda); 77.5% females and 22.5% males; more widows (38.0%) than married (35.5%). HIV/AIDS prevalence generally decreased with increasing level of education. The highest (66.7%) HIV/AIDS prevalence was recorded in Bushenyi, followed by 58.4% in Masaka, 57.9% in Mbarara and 53.3% in Rukungiri. Rukungiri patients above 60 years of age harboured 57.1% HIV/AIDS followed by 45.5% among Masaka patients aged 11 - 20 years and 40% among Mbarara patients less than 10 years of age. HIV/AIDS prevalence was significantly (p<0.05) dependent on socio-economic and demographic factors of surveyed population. Therefore socio-economic and demographic factors underlie HIV/AIDS prevalence in this region. Observed differences in prevalence of HIV/AIDS between the surveyed districts were remarkable and warrant regular surveillance for updated disease epidemiology. Education can debunk the generally misconstrued roles of social, economic and demographic factors in the spread of HIV/AIDS.