Theories of the relation between age at lesion onset and outcomes posit different views of the young brain: resilient and plastic (i.e., the so-called "Kennard Principle"), or vulnerable (i.e., the Early Vulnerability Hypothesis). There is support for both perspectives in previous research and questions about the "best" or "worst" times to sustain brain injury remain. Here, we present a systematic review investigating the influence of age at focal brain lesion onset on cognitive functioning. This systematic review identifies and qualitatively synthesizes empirical studies from 1985 to 2021 that investigated age at lesion onset as a variable of interest associated with neuropsychological outcomes. A total of 45 studies were identified from PubMed, PsycINFO, and CINAHL databases. Almost all studies indicated that brain injury earlier in the developmental period predicts worse cognitive outcomes when compared to onset either later in the developmental period or in adulthood. More specifically, the overwhelming majority of studies support an "earlier is worse" model for domains of intellect, processing speed, attention and working memory, visuospatial and perceptual skills, and learning and memory. Relatively more variability in outcomes exists for domains of language and executive functioning. Outcomes for all domains are influenced by various other age and injury variables (e.g., lesion size, lesion laterality, chronicity, a history of epilepsy). Continued interdisciplinary understanding and communication about the influence of age at lesion onset on neuropsychological outcomes will aid in promoting the best possible outcomes for patients.