Introduction: Rotavirus (RV) infection is the leading cause of severe diarrhea in children worldwide. It is responsible for around 25% of gastroenteritis (GE) cases, 33% of hospitalized GE cases, and an annual mortality rate of 113.4/100,000 in children < 5 years of age in Peru. RV infant vaccination is recommended by the World Health Organization and provides the best public health strategy to manage the disease. Universal RV vaccination was introduced in Peru in 2009. Methods: Trends in GE ambulatory visits, hospitalizations, and deaths in children < 5 years of age are described in the pre-vaccination (2004–2008) versus post-vaccination (2010–2018) periods. Time-trend analysis was performed (using generalized linear regression models) to assess the impact of vaccination nationwide and by region after adjusting for variables. Results: Between 2009 and 2011, vaccination coverage increased to over 80% in Peru. In infants < 1 year of age, GE ambulatory cases, hospitalizations, and deaths decreased in the post-vaccination period by 40.3%, 46.2%, and 55.5%, respectively (and in children < 5 years of age, by 34.4%, 41.9%, and 54.3%, respectively) compared with the pre-vaccination period. Results of the multivariate time-trend analysis also found significant decreases in the post-vaccination period of 10.7% (GE ambulatory cases), 17.2% (GE hospitalizations), and 37.3% (GE mortality) in children < 5 years of age. Data analyzed by region varied, with Costa and Sierra regions generally in line with the national findings; however, some findings were less robust for Selva due to fewer available data. Conclusion: After 9 years of RV vaccination in Peru, there appears to be a statistically significant positive impact of vaccination, in terms of reducing GE-related mortality, hospitalizations, and ambulatory visits in infants and young children. For policymakers to understand regional differences and future vaccination needs, continued improvement in surveillance is needed. Graphical Abstract: [Figure not available: see fulltext.]