Background <p>Antimicrobial resistance (AMR) is a critical global health threat, exacerbated by irrational prescribing, particularly in low-resource settings like Ethiopia. A significant gap persists between guideline knowledge and clinical practice, necessitating a deeper understanding of behavioral determinants influencing prescribing decisions.</p> Methods <p>This mixed-methods study employed a convergent parallel design in Addis Ababa, Ethiopia. Quantitative surveys were conducted with 270 prescribers including physicians, health officers and other health care providers with prescribing role, assessing prescribing behavior and Theoretical Domains Framework (TDF)-aligned determinants. Qualitative interviews with 12 clinicians (health care professionals with prescribing role and clinical pharmacists with recommending role) explored behavioral factors. Data were analyzed using regression, t-tests, and thematic analysis, followed by triangulation and Behavior Change Wheel (BCW) application to identify intervention targets.</p> Results <p>The study achieved a 98.18% response rate. The prevalence of inappropriate prescribing behavior is 19.26%. Quantitative analysis showed “Environmental Contexts/Resources” as the lowest TDF domain. “Knowledge” and “Social/Professional Role” positively predicted appropriate prescribing, while “Emotion” showed a negative association. Qualitative findings revealed experience-based decision-making, hierarchical influences, patient pressures, systemic constraints, and guideline barriers. Triangulation confirmed these findings, highlighting how strong knowledge can coexist with non-adherence due to contextual factors. The BCW suggested multifaceted interventions targeting capability, opportunity, and motivation.</p> Conclusion <p>The prevalence of inappropriate antimicrobial prescribing behavior was 19.26%, which is lower than estimates reported in several previous studies from similar low- and middle-income settings .Inappropriate antimicrobial prescribing stems from a complex interplay of capability, opportunity, and motivation, explaining why education-focused stewardship programs are often insufficient. Effective stewardship requires comprehensive, multi-level interventions addressing not only knowledge gaps but also structural and behavioral determinants, including professional hierarchies, emotional decision-making, and practice habits. This integrated strategy, grounded in the BCW, directly targets the root causes of inappropriate prescribing for sustained AMR mitigation.</p>