Background: Sepsis, a life-threatening infection-induced inflammatory condition, has significant global health impacts. Timely detection is crucial for improving patient outcomes as sepsis can rapidly progress to severe forms. The application of machine learning (ML) and deep learning (DL) to predict sepsis using electronic health records (EHRs) has gained considerable attention for timely intervention. Methods: PubMed, IEEE Xplore, Google Scholar, and Scopus were searched for relevant studies. All studies that used ML/DL to detect or early-predict the onset of sepsis in the adult population using EHRs were considered. Data were extracted and analyzed from all studies that met the criteria and were also evaluated for their quality. Results: This systematic review examined 1942 articles, selecting 42 studies while adhering to strict criteria. The chosen studies were predominantly retrospective (n = 38) and spanned diverse geographic settings, with a focus on the United States. Different datasets, sepsis definitions, and prevalence rates were employed, necessitating data augmentation. Heterogeneous parameter utilization, diverse model distribution, and varying quality assessments were observed. Longitudinal data enabled early sepsis prediction, and quality criteria fulfillment varied, with inconsistent funding–article quality correlation. Conclusions: This systematic review underscores the significance of ML/DL methods for sepsis detection and early prediction through EHR data.