Importance Congenital Zika syndrome (CZS) can lead to a range of developmental and neurological issues, which increases the risk of early death. However, the all-cause and cause-specific mortality in children with CZS in the first 5 years of life remain unknown. Objective: To compare the hazard of all-cause and cause-specific mortality before age 5 years among children with and without CZS in Brazil. Design, Setting, and Participants This cohort study used nationwide linked routine data including all children born from January 2015 to December 2018 in Brazil. They were followed-up until age 5 years, death, or December 2020, whichever occurred first. All analysis were conducted in May 2024. Exposures Confirmed or probable cases of CZS. Main Outcomes and Measures All-cause and cause-specific deaths from respiratory, infectious and parasitic, and nervous system diseases were the outcomes. Hazard ratios (HRs), comparing children with and without CZS, for all and cause-specific mortality were estimated using Cox proportional hazard models adjusted for region and year of birth, maternal characteristics (age, education, race and/or ethnicity, and marital status), and sex of the newborn. The analysis was conducted in May 2024. Results: In total, there were 11 387 431 live births (5 832 594 male newborns [51.2%]). Of 3080 children notified as CZS cases, 444 (14.4%) died, including 154 (34.7%) from respiratory diseases, 152 (34.2%) from infectious and parasitic diseases, and 82 (18.5%) from nervous system diseases. Children with CZS were predominantly preterm (596 newborns [20.0%] vs 1 122 378 newborns [10.1%]) and had low birth weight (1095 newborns [35.7%] vs 805 373 newborns [7.1%]), compared with children without CZS. After controlling for confounders, children with CZS were 13.10 (95% CI, 11.86-14.46) times more likely to die in the first 5 years of life compared with those without the syndrome. The cause-specific mortality HRs were 30.28 (95% CI, 25.59-35.83) for respiratory diseases, 28.26 (95% CI, 23.85-33.48) for infectious and parasitic diseases, and 57.11 (95% CI, 45.23-72.11) for nervous system diseases. After excluding newborns who were preterm, low birth weight, and/or small for gestational age, the HRs for all-cause and cause-specific deaths were even higher. Conclusions and Relevance: In this cohort study, children born with CZS had strikingly higher risk of overall and cause-specific mortality. These findings may support the development of clinical protocols to prevent early mortality and improve survival in these children.