Objectives: This study aimed to investigate the etiology and risk factors of infertility among Omani couples aged 18–49 years. Methods: Subjects in this retrospective cross-sectional study were selected using purposive sampling method from Omani couples who attended the infertility clinic of a tertiary referral hospital in Muscat between January 2015 and December 2022. Demographic variables, clinical findings, imaging results, hormonal profiles, surgical history, and semen parameters extracted from the hospital information system were analyzed. The main outcomes included male and female infertility etiologies and associated risk factors. Results: The participants included 259 Omani couples. Female-factor infertility accounted for 53.7% of cases, male-factor infertility for 41.7%, and unexplained infertility for 4.6%. Combined factors accounted for 14.3%. Among couples with primary and secondary infertility, mean ages of the female partners age were 37.0 ± 7.1 years and 43.0 ± 5.5 years respectively. Overall, 39.6% of women were obese or overweight. Polycystic ovarian syndrome (PCOS) (21.6%), fibroids (16.0%), endometriosis (7.8%), and tubal block (14.4%) were the main female factors. There was a significant association between body mass index and PCOS and between higher age and fibroids (r = 0.211; p < 0.010). Male abnormalities included oligospermia (45.4%), asthenozoospermia (18.5%), multiple semen abnormalities (23.1%), azoospermia (11.1%), and teratozoospermia (1.9%). Conclusions: Higher maternal age, high body mass index, particularly in association with PCOS and anovulatory disorders, were important modifiable risk factors of infertility in this cohort of Omani couples. Early identification and targeted interventions are recommended to improve fertility outcomes.