Yellow Fever (YF) is an infectious viral disease transmitted by Aedes mosquitoes that causes 200,000 human cases and 30,000 deaths annually in tropical Africa and South America. YF has emerged from its sylvatic cycle in the Kedougou region in Senegal regularly over the past five decades without any major urban outbreaks, but changes have occurred since 2007, including gold mining, increased urbanization and massive immigration.  Such changes have the potential to disrupt on the epidemiological pattern of YF in this region. We report results of surveillance and YFV outbreaks among humans, non–human primates and mosquitoes in Kedougou, Senegal during 2010 and 2011. Serum samples were collected from, 9,213 patients recruited from 7 clinics in Kedougou region and 13 confirmed and 10 probable YF cases were diagnosed. We also detected YF virus in 67 pools of mosquitoes, mainly Aedes furcifer, from September to December 2010, and evidence of recent infection was found in monkeys at the same period. Entomological investigations during the YF outbreak showed that epidemic vectors were found in the domestic context and entomologic risk indexes were well above the epidemic threshold. These data emphasize the concern that gold mining and associated changes occurred in Kedougou region could lead to emergence and propagation of YF human outbreaks.