The aim of this research was to elucidate potential barriers and facilitators to human papillomavirus (HPV) vaccination in Malawi, a sub-Saharan country. In Malawi, approximately 31 out of every 100,000 women develop cervical cancer annually, and 80% of those affected die from this malignancy. HPV vaccination may provide a feasible strategy for cervical cancer prevention in Malawi. However, important questions and concerns regarding cervical cancer and HPV vaccination acceptance among individuals and their communities must be considered prior to vaccine delivery. Qualitative interviews were conducted with 30 Malawian mothers aged 18–49 years from Chiradzulu District. Women’s knowledge and beliefs about HPV, cervical cancer, and vaccination, and their social-ecological contexts were explored in-depth. Thematic analyses revealed that despite women’s limited knowledge, cervical cancer was perceived to be a serious disease. Participants believed that as women, they were responsible for their children’s health. Women unanimously reported that they would vaccinate their children against HPV, especially if a health professional recommended it. Malawi’s health care infrastructure could present challenges to HPV vaccine programs; however, participants did not typically report this to be a barrier to vaccination. These data shed light on factors that may influence HPV vaccination acceptance and uptake in Malawi.