The article presents the results of flotation beneficiation experiments for polymetallic ore of complex mineralogical composition with the use of alkylbenzenesulfonic acid (ABSA) as a frothing reagent. Additional experiments showed the highest efficiency of ABSA application for samples of mixed-type ores, showing a significant increase in the recovery of gold, copper, zinc, and lead in the collective concentrates of flotation beneficiation. The use of an ABSA activator promotes the additional cleaning of fragments containing valuable metals from oxide films and coatings, as well as the transfer of microparticles of valuable metals due to the adsorption properties of organics and the formation of metal–carbon bonds. Another effect of this reagent use is an increase in the mass yield of concentrate while maintaining the quality parameters. Gold recovery in the main collective flotation concentrate more than doubled from 46.81 to 97.06%; copper recovery increased from 67.5 to 90.8%, zinc from 22.04 to 58.81%; and lead from 51.13 to 81.1% during the beneficiation process of polymetallic ore with the use of ABSA. A similar effect was observed for beneficiation of copper ore with complex composition; copper recovery in the main concentrate increased from 33.57 to 87.61%. Selective flotation with the development of gold concentrate from difficult-to-beneficiate polymetallic ore also showed a significant increase in gold recovery from 60.41 to 90.24% with ABSA pretreatment.