Background: Thyroid dysfunction is closely associated with psychiatric disorders, particularly Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). Alterations in thyroid hormones may mimic or exacerbate psychiatric symptoms, leading to diagnostic and therapeutic challenges. This study assessed thyroid disorders among patients diagnosed with MDD and GAD attending a tertiary hospital in Maiduguri, Nigeria. Methods: A comparative cross-sectional study was conducted among 300 participants comprising 100 patients with MDD, 100 patients with GAD, and 100 healthy controls. Sociodemographic data, psychiatric diagnoses based on DSM-5 criteria, and thyroid function tests (TSH, FT3, FT4) were obtained. Thyroid dysfunction was categorized into hypothyroidism, hyperthyroidism, subclinical hypothyroidism, and euthyroidism. Data were analyzed using SPSS version 26. Chi-square, ANOVA, and logistic regression were applied. Statistical significance was set at p < 0.05. Results: The prevalence of thyroid dysfunction was significantly higher among MDD patients (38%) and GAD patients (29%) compared with healthy controls (10%) (p < 0.001). Subclinical hypothyroidism was the most common abnormality among MDD patients (20%), while hyperthyroidism predominated among GAD patients (12%). Mean serum TSH was significantly elevated among MDD participants compared with controls (4.92 ± 2.11 vs 2.31 ± 1.08 mIU/L; p < 0.001). Logistic regression showed that female sex, age >40 years, and severity of psychiatric symptoms independently predicted thyroid dysfunction. Conclusion: Thyroid dysfunction is significantly associated with MDD and GAD among patients attending a tertiary hospital in Maiduguri. Routine thyroid screening should be incorporated into psychiatric evaluation to improve diagnosis and treatment outcomes.