Objectives: We sought to assess the complications and challenges facing the management of β-thalassemia major (β-TM) in Iraq. Methods: A total of 150 consecutive patients with β-TM who were registered at a main thalassemia center in Northern Iraq were enrolled in the study. The patients had their records reviewed, were clinically evaluated, and investigated for various complications. Results: Our patient cohort had a median age of 13 years (range: 1–35 years) and a male to female ratio of 1:1.2. Their median serum ferritin was 2762 µg/L, all were on regular transfusions, 94.7% were on chelation therapy, and 38.0% were splenectomized. Pre-transfusion hemoglobin levels were ≥ 9.0 g/dL in 38.7% of the patients. Short stature was encountered in 33.9% of those aged ≤ 20 years, and skeletal changes were noted in 50.7%. Iron overload associated complications, including hypogonadism, hypothyroidism, hypoparathyroidism, diabetes mellitus, and heart failure, were encountered in 52.8%, 7.3%, 3.3%, 3.3%, and 2.7%, respectively. Hepatitis C virus (HCV) antibodies were detectable in 35.3%, while HIV antibodies and hepatitis B surface antigen were not detectable in any. Patients with diabetes mellitus, heart failure, HCV antibodies, and hypoparathyroidism were significantly older than those without these complications. Hypogonadism was the only complication associated with significantly higher serum ferritin levels. Hypogonadism, heart failure, HCV antibodies, and diabetes were significantly more frequent among the splenectomized patients. Conclusions: The management of β-TM in this cohort of Iraqi patients is still suboptimal, and the need to ensure timely transfusions and optimize chelation, as well as a more robust iron overload assessment, should be underscored.