This study presents the results of a laboratory investigation conducted to evaluate the efficiency of coal fly ash to control the formation of acid mine drainage (AMD) from mine waste. Site-specific materials, coal fly ash from Atikokan Thermal Generating Station and mine tailings from Musselwhite mine, were mixed at different proportions for the investigation of the drainage chemistry and the optimal mix using static testing (acid–base accounting) and kinetic (column) testing. The acid–base accounting (ABA) results indicated that the fly ash possessed strong alkaline (neutralization) potential (NP) and could be used in the management of reactive mine tailings, thus ensuring prevention of AMD in the long-term. Column tests conducted in the laboratory to further investigate long-term performance of fly ash in the neutralization and prevention of acid mine drainage from tailings similarly showed that mixing fly ash with mine tailings reduces dissolution of many heavy metals from tailings by providing alkalinity to the system. It was found that a fly ash to tailings mass ratio equal to or greater than 15% can effectively prevent AMD generation from Musselwhite mine tailings in the co-placement approach.