This study sought to examine the moderating roles of ethnic identity, acculturation, and religiosity on the relationship between pain-related injustice appraisal and chronic low back pain (CLBP) outcomes among a sample of Arab-Americans, who are an underrepresented population in prior pain research. The study also aimed to examine the mediating effect of pain-related injustice appraisal in the relationship between discrimination and CLBP outcomes. The sample included 96 Arab-American adults who completed an online survey concerning their CLBP. Multiple regression was used to examine the moderating role of ethnic identity, acculturation, and religiosity on the relationship between injustice appraisal and disability and depression. Findings showed that ethnic identity (β = 0.43, p = 0.03) and religiosity (β = 0.28, p = 0.04), but not acculturation, buffered the relationship between pain-related injustice appraisal and CLBP-related depressive symptoms. Perceived discrimination predicted higher pain intensity (β = 0.28), disability (β = 0.56), and depressive symptoms (β = 0.51). Pain-related injustice appraisal significantly mediated the relationship between discrimination and CLBP-related disability (β = 0.24, p < 0.0001), and depressive symptoms (β = 0.22, p < 0.0001). The current study is the first to examine the role of unique ethnic characteristics, namely ethnic identity, acculturation, and religiosity, within the context of pain-related injustice appraisal. The results support the role of broader sociocultural and societal factors, such as ethnic-based discrimination, within the context of pain-related injustice appraisal as well as the influence of intra- and interpersonal factors and their interactions on pain-related injustice appraisal. PERSPECTIVE: This study is the first to demonstrate the unique role of ethnic identification, acculturation, and religiosity within the concept of pain-related injustice appraisal, specifically among Arab-Americans with chronic low back pain. This understanding could potentially help basic researchers, clinical scientists, as well as clinicians.