Background: Breast cancer is the leading cancer among women in Kenya, with late-stage presentation contributing significantly to high morbidity and mortality. Self-breast examination (SBE) is a cost-effective screening method for early detection, yet its uptake remains low, particularly in rural and sub-county healthcare settings. This study investigated the determinants of SBE practice among women attending the family planning clinic at Chuka Level 5 Hospital, Tharaka Nithi County, Kenya. Methods: An analytical cross-sectional design utilizing a mixed-methods approach was conducted. A total of 129 women were selected through systematic random sampling, while six healthcare providers (nurses, clinical officers, and gynecologists) were purposively sampled for key informant interviews. Data were gathered using researcher-administered questionnaires and structured interview schedules. Quantitative data were analyzed using SPSS v29 using descriptive statistics, Chi-square tests, and logistic regression analysis. Qualitative data underwent thematic analysis. Results: The mean age of participants was 26.03 ± 7.46 years (range 18–54), with 54.3% residing in rural areas and 55.9% having attained tertiary education. The prevalence of SBE practice was 66.1%; however, only 52.4% performed it on a monthly basis, and 47.6% performed it at the recommended time after menstruation. Primary reasons for non-performance included lack of awareness of correct steps (30.0%) and forgetfulness (27.9%). Women with primary education were significantly more likely to perform SBE compared to those with tertiary education (AOR = 0.247, 95% CI: 0.101–0.608, p = 0.002). Farmers were 4.48 times more likely to perform SBE than women in formal employment (AOR = 4.48, 95% CI: 1.31–15.29, p = 0.017). Overall knowledge of SBE was moderate (mean 69.88%), with 38.6% demonstrating good overall knowledge. Family encouragement significantly promoted SBE uptake (AOR = 0.345, 95% CI: 0.148–0.806, p = 0.014).