Background: Infective endocarditis (IE) is associated with significant neurological complications (NCs). The impact of neurological sequelae due to IE, however, is not well characterized. Thus, the aim of this systematic review and meta-analysis is to determine whether patients who experienced NCs from IE had worse outcomes compared to those without neurological complications. Methods: We conducted a systematic and comprehensive literature search of MEDLINE, Cochrane Library, Google Scholar, and BioMed Central (PROSPERO registration ID: CRD42024518651). Data on the primary outcome of all-cause mortality and the secondary outcome of surgical timing were extracted from 25 observational studies on patients with confirmed IE, both with and without NC. Results: In the pooled total of patients with IE, NCs were present in 23.7% (60.8% ischaemic stroke and 16.4% haemorrhagic stroke). All-cause mortality was significantly higher in patients with IE and NCs (OR 1.78, CI 1.47–2.17, p < 0.0001) compared to those without, particularly in those with major neurological events (OR 2.18, CI 1.53–3.10, p < 0.0001). Conversely, minor or asymptomatic strokes showed no significant correlation with mortality (OR 1.10, CI 0.82–1.47, p = 0.543). There was no significant difference in the timing of surgical intervention (standardized mean difference −0.53, CI −1.67 to 0.61, p = 0.359) between the two patient groups. Conclusions: Major NCs due to infective endocarditis were associated with a significantly increased all-cause mortality. This underscores the critical importance of early recognition and management strategies tailored to the severity of neurological events.