To strengthen the understanding of rheumatic diseases (RDs) as the most common underlying conditions associated with acquired hemophilia (AH), a potentially fatal bleeding condition due to the development of autoantibodies or inhibitors to coagulation factor VIII, and rarely to factor IX, here we presented two cases of RDs associated AH to elucidate the disease progression, treatment, and prognosis. The presented 2 cases showed good responses to glucocorticoid (GC) and immunosuppressive agents. And then, a case-based systematic review was conducted to better understand the clinically practiced diagnosis and treatment of RDs associated AH. A total of 14 articles were included in the final literature review. All the identified 14 patients with underlying RDs and AH presented with bleeding symptoms, increased APTT, decreased FVIII activity, and positive FVIII inhibitors. Twelve of the 14 patients (85.7%) started an eradication of autoantibodies treatment with GC and immunosuppressive agents. Among which six patients achieved partial or complete remission, and four patients (28.6%) switched to Rituximab and responded well. Nine of the 14 patients received hemostasis therapy, including recombinant human FVIIa (rFVIIa). Two patients (14.3%) died due to mass bleeding and key organ failure. AH should be highly suspected in patients with RDs presenting spontaneous mucocutaneous or internal bleeding and an isolated prolonged APTT. Given the high morbidity of AH, it is important to facilitate efficient and proper management.