The burden of Sexually transmitted infections (STIs) remains a public health problem that should be addressed considering its effect on society and close association with HIV. This study aimed to determine the knowledge and prevalence of common STIs and associated risk factors among adult patients seeking STI care in health facilities in Ho Municipality. This was an analytical cross-sectional study involving 178 adult clients seeking treatment for suspected STIs, from November 2020 to April 2021. Data on participants' demographic characteristics, knowledge and health-seeking behaviour for STI therapy was obtained. Urine and blood samples were also taken from each participant for microbiological screening to identify the infecting pathogen and the specific STI. Multiple logistic regression and chi-square analyses were used to test the significance of associations. Of the 178 participants, 71.91% (n = 128) were women and 61.24% (n = 109) were unmarried. About 13% (n = 23) had poor knowledge of STIs. Prevalence of the STIs was 24.72% (n = 44) of which gonorrhoea was the highest 11.24% (n = 20), followed by chlamydia 10.11% (n = 18) and syphilis 7.30% (n = 13). Of all the participants, 3.37% (n = 6) had co-infections with at least 2 pathogens. Infection with all three pathogens was observed in a single participant. Participants who were married were associated with 61% reduced odds of sexually transmitted infection compared to participants who were unmarried (AOR = 0.39; Cl = 0.17-0.89). Participants who smoked had 6.5 times increased odds of the infection compared to nonsmoking participants (AOR = 6.51; Cl = 1.07-39.56). Although knowledge of STIs was high, it did not appear to contribute to lowering of the prevalence. This suggests there may be other factors other than awareness or knowledge driving STIs. There is an urgent need for further studies to ascertain the drivers of STIs beyond knowledge and awareness in the public.