Neglected tropical diseases (NTDs) with skin manifestations present a significant health and societal problems challenge worldwide. This study aimed to analyzed factors associated with the knowledge, attitudes and practices (KAPs) of primary healthcare workers (HCW) concerning NTDs with skin manifestations in the Dakar region of Senegal. We conducted a cross-sectional study utilizing a semi-structured questionnaire which was administered to eligible HCW (general practitioners, nurses and midwives) working at the 24 health centers located in the Dakar region. Data were collected using the ODK Collect application (version 2022.3.6). KAPs measures were constructed from questionnaire responses, and bivariate analysis was used to identify associated factors. Of the 187 HCW surveyed, 75.9% were female, with a mean age of 35.1 years (SD: 8.56). The majority of HCWs had a bachelor’s degree (40.6%), were nurses (49.2%) and had between 1- and 10-years of professional experience (52.4%). Regarding their knowledge of NTDs with skin manifestations, only 43.3% of HCW had received initial training on NTDs. The most commonly reported NTDs with skin manifestations were leprosy (53.5%), lymphatic filariasis (51.3%), scabies (49.7%), onchocerciasis (45.5%) and schistosomiasis (42.8%). Television was the main source of information about these NTDs (38.5%). In term of practices, only 47.6% of HCW reported being able to diagnose NTDs with skin. Factors associated with good knowledge regarding NTDs with skin manifestations included having received training on NTDs (p = 0.0015) and more years of professional experience (p = 0.004). In summary, there is a need to strengthen and raise awareness about NTDs with skin manifestations among HCWs and promote quality management of patients in Senegal.