Given the lack of literature on Undergraduate African American females in the sciences (UAAFS), this study sought to explicate their experiences at one large, predominantly White, Research I institution in the southwestern United States. In particular, the purpose of this study was to identify factors that affect the academic success and persistence of Black females in the natural and physical sciences. Data was collected via in-depth, semi-structured interviews with 15 Black female science majors. Findings from this study identified several supportive mechanisms for academic success: family, religion, teaching assistants and friends. Also identified were seven barriers to academic success: employment, lack of diversity, cultural dissonance, unwelcoming Research I environment, faculty, advisors, classmates, and lab groups. Further, an analysis of students' responses revealed numerous instances of racial and gender micro-aggressions. Recommendations are provided to address factors identified as affecting student academic success and persistence as well as a culture of micro-aggressive behavior.