Vector-borne diseases (VBDs) may be transmitted among humans, domestic animals, and wildlife, with cattle in particular serving as an important source of exposure risk to humans. The close associations between humans and cattle can facilitate transmission of numerous VBDs which can impact nations’ public health and economic security. Published studies demonstrate that cattle can influence human exposure risk positively, negatively or have no effect. There is a critical need to synthesize the information in the scientific literature on this subject, in order to illuminate the various ecological mechanisms that can affect the risk of humans contracting VBDs from cattle. Therefore, the aim of this systematic review was to review the scientific literature, provide a synthesis of the possible effects of cattle on VBD risk to humans, and propose future directions for research. This study was performed according to the PRISMA 2020 extension guidelines for systematic review. After screening 470 peer-reviewed articles published between 1999 – 2019 using the databases Web of Science Core Collection, PubMed Central, CABI Global Health, and Google Scholar, and utilizing forward and backward search techniques, we identified 127 papers that met inclusion criteria. Results of the systematic review indicate that cattle can be beneficial or harmful to human health with respect to VBDs depending on vector and pathogen ecology and livestock management practices. Cattle can increase risk of exposure to infections transmitted by tsetse flies and ticks, followed by sandflies and mosquitoes, through a variety of mechanisms. However, cattle can have a protective effect when the vector prefers to feed on cattle instead of humans and when chemical control measures (e.g., acaricides/insecticides), semio-chemicals, and other integrated vector control measures are utilized in the community. We highlight that further research is needed to determine ways in which these mechanisms may be exploited to reduce VBD risk in humans.