Objective: To investigate the joint impact of tinnitus-related distress (TRD), anxiety, depressive symptoms, and other somatization symptoms on health-related quality of life (HRQoL) in female vs. male patients with chronic tinnitus. Method: Three-hundred-and-fifty-two patients with chronic tinnitus completed audiological testing and a psychological assessment battery that comprised—among other measures—German versions of the Tinnitus Questionnaire, Hospital Anxiety and Depression Scale, Somatic Symptom Scale-8, and Health-Related Quality of Life scale. Descriptive analyses examined associations as well as within- and between-gender differences of the measured variables. Gender-specific serial indirect effects analyses aimed to explain the impact of TRD on HRQoL through psychological processes, notably anxiety, depressive symptoms, and somatization symptoms. Results: Both female and male patients yielded lower mental than physical HRQoL and negative associations between the measured psychological variables and HRQoL. Compared to male patients, female patients reported higher levels of tinnitus-related- and wider psychological distress, other somatization symptoms (e.g., headaches), and impairments in mental and physical HRQoL. For each gender, depressive symptoms, anxiety, and somatization symptoms fully mediated the effect of TRD on mental and physical HRQoL. A double-dissociation revealed an interaction of somatization symptoms and depression on the TRD-HRQoL association in women, and of somatization symptoms and anxiety in men. Conclusions: In patients with chronic tinnitus, psychological constructs account for reported impairments in both mental and physical HRQoL. To improve patients’ HRQoL, treatment conceptualizations should consider gender-specific psychological expressions of low mood or anxiety.