Background Multimorbidity is common in patients with breast cancer, thus increasing the complexity of cancer care and economic burden, worsening their prognosis and quality of life. The prevalence of multimorbidity and its influence on psychological distress among patients with breast cancer have not been well characterized. Objectives To examine the prevalence of multimorbidity and its associations with anxiety and depression among newly diagnosed patients with breast cancer. Methods We conducted a retrospective observational cohort study using a large administrative claims database. Patients with breast cancer (ICD-10-CM: C50.x) were identified during the study period (1/1/2017-12/31/2020). The index date was defined as the diagnosis date of breast cancer. Demographics and comorbid conditions were assessed using data within 12 months prior to the index date. Multimorbidity was defined as the presence of ≥2 comorbid conditions. Anxiety and depression were examined using data within 12 months after the index date. Multivariable logistic regressions were performed to examine the associations between multimorbidity and anxiety and depression, adjusting for sociodemographic factors. Results Of the 6392 patients with newly diagnosed breast cancer, 86.9% had multimorbidity at the time of breast cancer diagnosis. The median number of comorbid conditions was 5. Overall, 27.7% experienced anxiety, and 21.9% experienced depression in the first year following breast cancer diagnosis. An increased number of comorbid conditions was associated with elevated prevalence of both anxiety and depression. After adjusting for possible confounding factors, number of comorbid conditions was significantly associated with risk of anxiety (adjusted odds ratio [95% confidence interval (CI)]: 1.17 [1.15-1.19]), and depression (1.24 [1.21-1.26]); all P < .0001. Conclusions Multimorbidity was highly prevalent among patients with breast cancer and was strongly associated with increased risk of anxiety and depression in the first year following breast cancer diagnosis. The presence of multimorbidity, anxiety, and depression should be considered in the context of clinical decision making to optimize cancer care and improve mental health and quality of life.