Stored liquid dairy manure provides a conducive environment to microbial communities for methane (CH4) production. Significant reductions of emissions from these systems have been observed by using different management strategies and treatment technologies. However, knowledge on how microbial communities respond to the mitigation actions is lacking, and is important for developing and refining mitigation strategies. Using lab and meso-scale studies, the responses of microbial communities to varying levels of total solids content, residual slurry, pH, and chemical agents were assessed. Gas chromatography and laser-based trace gas analysis were used to monitor CH4 flux whereas molecular techniques including denaturing gradient gel electrophoresis, quantitative real-time PCR, and next generation sequencing of marker genes were used to study the microbes. With reduction of total solids content (9.5% to 0.3%), we found up to ~23% increases in the mean abundance and activity of methanogens. Cumulative CH4 emissions, however, decreased by ~70% as total solid levels decreased. These results indicated that available carbon substrate, and not methanogen abundance, may be limiting cumulative CH4 emissions at reduced total solids of dairy slurries. In a follow-up study, abundant bacterial and methanogenic communities were detected, and related to significant increases in cumulative CH4 emissions from stored dairy slurries with 10% and 20% residual slurry. The presence of residual slurry, did not alter the core methanogenic phylotypes, although, Methanocorpusculum predominated the methanogen population, RNA data indicated that methanogens related to Methanosarcina were the major players in CH4 production. Microbial communities in residual slurries may be reduced by chemical treatments. In a lab-scale study, significant reductions in the abundance of methanogens (up to ~28%) were observed when sodium persulfate, potassium permanganate, or their combination with sodium hypochlorite. In slurries treated with H2SO4, the abundance of methanogen populations was not impacted. In a subsequent pilot-scale study, the transcriptional activities of methanogen populations and CH4 production were significantly affected by acidification of manure. Taken together, the findings of these studies suggest that the activity responses of slurry microorganisms can help in the refinement and/or development of effective mitigation strategies.