Caring plays a vital role in nursing and serves as an indicator of quality. Nurse caring behaviors are directed towards patients' safety and wellbeing. Nurses' perceptions of caring behaviors are affected by different factors. Understanding the factors linked to how nurses perceive caring behaviors is crucial for enhancing the quality of care. The aim of this study was to examine the factors associated with nurses' perceptions of caring behaviors and gain a more comprehensive understanding. A multicenter sequential explanatory mixed-methods study was conducted among medical-surgical nurses at three referral hospitals in the Amhara region, Ethiopia. Quantitative data were collected using a pretested self-administered survey package including the Amharic version of the Caring Behaviors Inventory-16. Qualitative interviews using semi-structured, open-ended questions were conducted after the survey to complement and clarify the quantitative results, facilitating integrate through a connecting approach. A multiple linear regression model was used to examine the relationship between nurses' perceptions of caring behaviors and associated factors. The qualitative data was examined to find meaningful patterns using codebook thematic analysis. This method was deductive and followed the guidelines by Braun and Clarke, building on the findings from the quantitative results. The overall mean of nurses' perceptions of caring behaviors was 4.75. The multiple linear regression analysis showed that female sex (b = 0.300, P = 0.004), age (b = 0.028, P = 0.001), nurse staffing (b=-0.115, P = 0.001), work-related stress (b = 0.298, P = 0.003), and job satisfaction (b=-0.254, P = 0.016) were associated with nurses' perceptions of caring behaviors. The codebook thematic analysis generated three themes, caring is universal and fundamental in nursing, impediments to provision of comprehensive care, and perception of the work conditions. The findings of the qualitative data complemented the results of the quantitative data. Discrepancies between nurses' expectations and the actual working environment may create uncertainty in care provision and impact quality-of-care. Strategies to harmonize the nurses' working environment should consider work-related factors.