Background Implementing effective self-care practices for non-communicable diseases (NCD) prevents complications and morbidity. However, scanty evidence exists among patients in rural sub-Saharan Africa (SSA). We sought to describe and compare existing self-care practices among patients with hypertension (HTN) and diabetes (DM) in rural Uganda. Methods Between April and August 2019, we executed a cross-sectional investigation involving 385 adult patients diagnosed with HTN and/or DM. These participants were systematically randomly selected from three outpatient NCD clinics in the Nakaseke district. Data collection was facilitated using a structured survey that inquired about participants’ healthcare-seeking patterns, access to self-care services, education on self-care, medication compliance, and overall health-related quality of life. We utilized Chi-square tests and logistic regression analyses to discern disparities in self-care practices, education, and healthcare-seeking actions based on the patient’s conditions. Results Of the 385 participants, 39.2% had only DM, 36.9% had only HTN, and 23.9% had both conditions (HTN/DM). Participants with DM or both conditions reported more clinic visits in the past year than those with only HTN (P = 0.005). Similarly, most DM-only and HTN/DM participants monitored their weight monthly, unlike those with only HTN (P<0.0001). Participants with DM or HTN/DM were more frequently educated about their health condition(s), dietary habits, and weight management than those with only HTN. Specifically, education about their conditions yielded adjusted odds ratios (aOR) of 5.57 for DM-only and 4.12 for HTN/DM. Similarly, for diet, aORs were 2.77 (DM-only) and 4.21 (HTN/DM), and for weight management, aORs were 3.62 (DM-only) and 4.02 (HTN/DM). Medication adherence was notably higher in DM-only participants (aOR = 2.19). Challenges in self-care were significantly more reported by women (aOR = 2.07) and those above 65 years (aOR = 5.91), regardless of their specific condition(s). Conclusion Compared to rural Ugandans with HTN-only, participants with DM had greater utilization of healthcare services, exposure to self-care education, and adherence to medicine and self-monitoring behaviors. These findings should inform ongoing efforts to improve and integrate NCD service delivery in rural SSA.