Microorganisms interact in complex communities, affecting microbially-mediated processes in the environment. Particularly, aerobic methanotrophs showed significantly stimulated growth and activity in the presence of accompanying microorganisms in an interaction network (interactome). Yet, little is known of how the interactome responds to disturbances, and how community functioning is affected by the disturbance-induced structuring of the interaction network. Here, we employed a time-series stable isotope probing (SIP) approach using 13C–CH4 coupled to a co-occurrence network analysis after Illumina MiSeq sequencing of the 13C-enriched 16S rRNA gene to directly relate the response in methanotrophic activity to the network structure of the interactome after desiccation-rewetting of a paddy soil. Methane uptake rate decreased immediately (<5 days) after short-term desiccation-rewetting. Although the methanotroph subgroups differentially responded to desiccation-rewetting, the metabolically active bacterial community composition, including the methanotrophs, recovered after the disturbance. However, the interaction network was profoundly altered, becoming more complex but, less modular after desiccation-rewetting, despite the recovery in the methanotrophic activity and community composition/abundances. This suggests that the legacy of the disturbance persists in the interaction network. The change in the network structure may have consequences for community functioning with recurring desiccation-rewetting.