Background Condom use, especially at first sex for unmarried people, is an important behaviour that reduces the risk of HIV transmission, and other Sexually Transmitted Diseases (STDs), as well as unwanted pregnancies. In reviewing the literature, little information was found to elucidate the spatial context of condom use among people who had an early sexual debut. Understanding factors that influence no condom use at first sex in different local or geographical areas can add value in addressing these risky first-sex practices and minimise the risk of getting HIV, STDs, and unwanted pregnancies in South Africa, especially among young people. Therefore, this paper aimed to determine the spatial heterogeneity of factors associated with no condom use at first sex in South Africa using Geographically Weighted Regression (GWR) with Poisson distribution and local bivariate relationships. Methods This article used data from the fifth South African National HIV Prevalence, HIV Incidence, Behaviour and Communication Survey (SABSSM V) of 2017. Spatial autocorrelation, GWR using Poisson distribution, and local bivariate relationships were undertaken using ArcGIS Pro. Results Geographically weighted regression using Poisson distribution results highlighted being female, being young, having never married, being unemployed, having sexual debut at a younger age, having two or more sexual partners, having no risk of being infected with HIV, and having good Self-perceived Health (SPH) to be significant factors influencing no condom use at first sex, with pseudo R2 = 0.96 and AICc = 692. Local bivariate relationships showed the relationship between no condom use at first sex and most explanatory variables to exhibit a positive linear relationship in most districts with the exception of having never married, which showed a positive linear relationship in only 18 districts, while 33 districts showed a concave relationship. These relationships were all significant with p < 0.05. Conclusion This localised analytical approach may contribute to the development of geo-targeted interventions and policies tailored to specific regions within South Africa, thereby improving the effectiveness of efforts to promote safe first sexual practices. Educational programs targeting youth should be developed to further raise awareness of the risks associated with unprotected sex and the importance of condom use. More efforts should be made to break the barriers, such as sexual relationship power, gender, and sociocultural and religious influences, which tend to put young, never-married, and unemployed women at risk of no condom use at first sexual debut. It is further recommended that the type of relationship between no condom use at first sex and each explanatory factor at the local region be considered during geo-targeted interventions as this will assist in the type of intervention and duration of intervention.