Controlling hydrogen sulfide (H2S) odors and emissions using a single, effective treatment across a town-scale sewer network is a challenge faced by many water utilities. Implementation of a sewer diversion provided the opportunity to compare the effectiveness of magnesium hydroxide (Mg(OH)2) and two biological dosing compounds (Bioproducts A and B), with different modes of action (MOA), in a field-test across a large sewer network. Mg(OH)2 increases sewer pH allowing suppression of H2S release into the sewer environment while Bioproduct A acts to disrupt microbial communication through quorum sensing (QS), reducing biofilm integrity. Bioproduct B reduces H2S odors by scouring the sewer of fats, oils and grease (FOGs), which provide adhesion points for the microbial biofilm. Results revealed that only Mg(OH)2 altered the microbial community structure and reduced H2S emissions in a live sewer system, whilst Bioproducts A and B did not reduce H2S emissions or have an observable effect on the composition of the microbial community at the dosed site. Study results recommend in situ testing of dosing treatments before implementation across an operational system.