Abstract Background Chronic non-communicable diseases (CNCDs) are an urgent public health issue in China, especially among older adults. Hence, self-management is crucial for disease progression and treatment. Electronic health (e-health) literacy and self-efficacy positively correlate with self-management. However, we know little about their underlying mechanisms in older adults with CNCDs. Objective To explore the factors that influence chronic disease self-management (CDSM) and verify self-efficacy as the mediator between e-health literacy and self-management behavior in older patients with CNCDs. Methods This cross-sectional study included 289 older patients with CNCDs from Hunan province, China, between July and November 2021. E-health literacy, self-efficacy, social support, and CDSM data were collected through questionnaires. The influence of each factor on CDSM was explored with multiple linear regression analysis. Intermediary effects were computed via a structural equation model. Results The total CDSM score in the patients was 29.39 ± 9.60 and only 46 (15.92%) patients used smart healthcare devices. The regression analysis showed e-health literacy, self-efficacy, and social support were the factors that affected CDSM. Furthermore, the structural equation model revealed that self-efficacy directly affected CDSM ( β  = 0.45, P  < 0.01), whereas e-health literacy affected it directly ( β  = 0.42, P  < 0.01) and indirectly ( β  = 0.429, P  < 0.01) through self-efficacy. Conclusions This study revealed that self-management among older patients with CNCDs is at a low level, and few of them use smart healthcare devices. Self-efficacy plays a partial intermediary role between e-health literacy and self-management in older patients with CNCDs. Thus, efforts to improve their CDSM by targeting e-health literacy may be more effective when considering self-efficacy.