Atrazine and S-metolachlor are two of the most widely used herbicides for agricultural purposes; consequently, residues of both compounds and their metabolites had been detected in ground and superficial waters. Unlike atrazine, the complete degradation of metolachlor has not been achieved. Hence, the purpose of this research is to study the biodegradation of a commercial mixture of atrazine and S-metolachlor in a prototype of a multi-channel packed-bed-biofilm reactor (MC-PBR) designed with the aim of solving the problems of pressure drop and oxygen transfer, typically found on this type of bioreactors. Because the removal efficiency of the herbicides was increased when Candida tropicalis was added to the original microbial community isolated, the reactor was inoculated with this enriched community. The operational conditions tested in batch and continuous mode did not affect the removal efficiency of atrazine; however, this was not the case for S-metolachlor. The removal rates and efficiencies showed a notable variation along the MC-PBR operation.