Our study provides substantial evidence that the host genome affects the comprehensive function of the microbiome in the rumen of bovines. Of 1,107/225/1,141 rumen microbial genera/metagenome assembled uncultured genomes (RUGs)/genes identified from whole metagenomics sequencing, 194/14/337 had significant host genomic effects (heritabilities ranging from 0.13 to 0.61), revealing that substantial variation of the microbiome is under host genomic control. We found 29/22/115 microbial genera/RUGs/genes host-genomically correlated (|0.59| to |0.93|) with emissions of the potent greenhouse gas methane (CH4), highlighting the strength of a common host genomic control of specific microbial processes and CH4. Only one of these microbial genes was directly involved in methanogenesis (cofG), whereas others were involved in providing substrates for archaea (e.g. bcd and pccB), important microbial interspecies communication mechanisms (ABC.PE.P), host-microbiome interaction (TSTA3) and genetic information processes (RP-L35). In our population, selection based on abundances of the 30 most informative microbial genes provided a mitigation potential of 17% of mean CH4 emissions per generation, which is higher than for selection based on measured CH4 using respiration chambers (13%), indicating the high potential of microbiome-driven breeding to cumulatively reduce CH4 emissions and mitigate climate change.