The goal of this systematic review was to examine the existing literature base regarding the factors impacting patient outcomes associated with use of emergency medical services (EMS) operating in urban versus rural areas. A specific subfocus on low and lower-middle-income countries was planned but acknowledged in advance as being potentially limited by a lack of available data. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed during the preparation of this systematic review. A comprehensive literature search of PubMed, EBSCO (Elton B. Stephens Company) host, Web of Science, ProQuest, Embase, and Scopus was conducted through May 2018. To appraise the quality of the included papers, the Critical Appraisal Skills Programme Checklists (CASP) were used. Thirty-one relevant and appropriate studies were identified; however, only one study from a low or lower-middle-income country was located. The research indicated that EMS in urban areas are more likely to have shorter prehospital times, response times, on-scene times, and transport times when compared to EMS operating in rural areas. Additionally, urban patients with out-of-hospital cardiac arrest or trauma were found to have higher survival rates than rural patients. EMS in urban areas were generally associated with improved performance measures in key areas and associated higher survival rates than those in rural areas. These findings indicate that reducing key differences between rural and urban settings is a key factor in improving trauma patient survival rates. More research in rural areas is required to better understand the factors which can predict these differences and underpin improvements. The lack of research in this area is particularly evident in low- and lower-middle-income countries.