ABSTRACT Heart failure (HF) is a long‐term, progressive chronic condition that significantly affects patients' quality of life (QoL) and burdens healthcare systems. This study examined the mediating role of general life satisfaction on the relationship between self‐care practices and QoL among patients with HF in Jordan. A cross‐sectional correlational design recruited 124 patients with HF conveniently from four governmental hospitals. Self‐care was assessed using the self‐care of heart failure index, quality of life was measured using the short form health survey, and life satisfaction was measured using the general life satisfaction scale. Mean scores for self‐care, subscales except for maintenance, were below 70, indicating inadequacy. Physical and mental QoL scores were 38.59 (SD = 5.82) and 31.34 (SD = 8.65), respectively. Self‐care and life satisfaction explained 32% of the variance in QoL. The Sobel test confirmed partial mediation through life satisfaction; life satisfaction partially mediates the link between self‐care and QoL. To conclude, clinicians should support both self‐care and psychosocial well‐being to enhance patients' QoL.