Introduction Retinoblastoma (RB) is the most common primary intraocular cancer of childhood. Over the last few decades, a variety of techniques and treatment modalities emerged that improved the survival and ocular salvage rate of patients with RB. We investigated the relative survival trends of patients with RB from 2000 to 2018 by using the Surveillance, Epidemiology, and End Results (SEER) database. Design Retrospective database review. Methods We extracted data from SEER 18 from 2000 to 2018. All patients with clinically diagnosed RB during the study period were included. We utilized SEER*Stat 8.3.9 and JPSurv software to estimate relative 5‐ and 10‐year survival rates and trends and generated descriptive analyses with IBM SPSS. Main Outcome Measures Patient survival rates at 5‐ and 10‐year after RB diagnosis. Results RB was diagnosed in 1479 patients within the SEER 18 Program during our study period. The cohort comprised 776 (52.5%) males, 615 (41.6%) non‐Hispanic whites, 487(32.9%) Hispanics, 1030 (69.6%) patients with unilateral disease, and 1087 (73.5%) patients with localized disease. Relative survival trends at 5‐ and 10‐year significantly declined over the study periods (−0.42%, and −0.50% annually, respectively) but the decline was not significant in unilateral and bilateral RB cases separately. Conclusions Five‐ and ten‐year relative survival trends declined from 2000 to 2018 and were significantly decreasing. Further studies that include more patients are needed to identify the factors contributing to reduced survival of patients with RB over time. Retinoblastoma was one of the success stories in pediatric oncology, with survival exceeding 98%. However, here we show a decline in the survival of retinoblastoma at the population level. This can be attributed to the new therapies practices in smaller centers with decentralization of services.