Early adolescence is a period characterized by enormous biological, cognitive, sexual, emotional, and social changes. Sexual curiosity and the desire to acquire sexual health (SH) information are part of these developments. Understanding the SH knowledge acquisition process is critical for designing interventions that can best support very young adolescents (VYAs). This study explored the SH knowledge acquisition processes among VYA girls aged 10 to 14 years who attended the DREAMs Girl Only Clubs (GOCs) and those who did not. The GOCs were a part of a larger comprehensive HIV prevention project called DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe) which provided an evidence-based core package of interventions to VYAs to prevent HIV. In-depth interviews were conducted with 43 VYA girls aged 10-14 years in two rural southern districts of Zomba and Machinga in Malawi. Twenty-three VYA girls were GOC participants and 20 VYAs were not. Guided by the Social Ecological Model, a thematic analysis approach was used to analyze the data with the assistance of Nvivo 12 software. The SH knowledge acquisition processes were the interaction of various factors at the microsystem (biological factors, attitudes), mesosystem (parents, older relatives, friends), and exosystem levels (schools and GOCs). Factors influencing this interaction included the beginning of menstruation, supportive parents/adults on SH issues, trust and confidentiality in SH information sources, and preference for well-informed sources of information. Compared to Non-GOC participants, GOC participants demonstrated an in-depth knowledge of SH issues, and positive sexual behaviors such as HIV testing. Limitations to SH knowledge acquisition were adult messages' focus on sexual relationship avoidance and on girls who have started menstruation; perception of adults not being knowledgeable about SH and school teachers hiding some SH information. VYA SH interventions that provide VYA with accurate SH information such as the GOCs have the potential to address the limitations that other sources have in reaching VYAs. Integrating such interventions with empowering parents, other adults, and teachers with comprehensive SH information and with skills on how to deliver SH information to VYAs can enhance their SH knowledge acquisition and influence positive behavior change.