This research study described the factors driving infectious disease outbreaks using Foot-and-mouth disease (FMD) in Uganda and Lyme disease in North Dakota (ND), Minnesota (MN) and Wisconsin (WI) as case studies. Retrospective data on FMD vaccines and outbreaks in Uganda (2001 – 2010) and Lyme disease in ND, MN and WI (1990 – 2011) was used. The time (7.5 weeks) taken to respond to FMD outbreaks, limited serotyping/subtyping (9/121) of outbreaks and the low percentage of cattle vaccinated (2.1 – 21.2%) portray ineffective control programs. Similarly, increase in fall temperature (P = 0.0189) and annual precipitation (P = 0.0250) were associated with increased human Lyme cases. Shrub land coverage and human population also increased in WI, MN and ND while forest coverage increased in ND. These favor tick and deer proliferation leading to increased human exposure to Lyme Borreliosis. Therefore ineffective disease control programs, climate and environment factors influence infectious disease occurrence.