Background: The human papilloma virus (HPV), a principal factor in the development of cervical cancer, is identified as one of the most widespread sexually transmitted infections, leading to a variety of conditions globally, from warts to cancer. It is estimated that 75% of people worldwide will contract an HPV infection at some point in their lives. Vaccination against HPV serves as an important preventive measure to reduce the rates of cervical cancer. Objective: This study assessed knowledge, attitude of mothers toward HPV vaccine uptake in Local communities in Edo State Nigeria. Methods: A cross-sectional study utilizing a descriptive approach was carried out with 350 participants, chosen through simple random sampling. Information was gathered via questionnaires conducted by researchers and was processed with the Statistical Package for the Social Sciences (SPSS), version 25. To examine the relationships between variables, the Fisher's exact test was employed, with statistical significance determined by a P-value < 0.05. Results: The average age of those surveyed was 40.4 years, with a standard deviation of 10.1 years. A mere 28.3% (44 respondents) had adequate knowledge about HPV and its vaccine. A significant portion (80%) exhibited a negative attitude toward receiving the HPV vaccine. There was a noticeable statistical correlation between the respondents' age and their awareness of HPV (with a p-value of 0.019) as well as between their employment status and their knowledge about HPV (p-value = 0.002). The primary reason cited by participants for not getting the HPV vaccine was its lack of availability. Conclusion: Knowledge and uptake of HPV vaccination among the respondents were poor. Majority also had negative attitude towards uptake of the vaccine.