Hijacking the cellular protein degradation system offers unique opportunities for drug discovery, as exemplified by proteolysis-targeting chimeras. Despite their great promise, it has so far not been possible to reprogram the bacterial degradation machinery to interfere with microbial infections. In our study, we develop small-molecule degraders, so-called BacPROTACs, that bind to the substrate receptor domain of the ClpC:ClpP protease, priming neo-substrates for degradation. In addition to their targeting function, BacPROTACs activate ClpC, transforming the resting unfoldase into its functional state, as visualized by cryo-EM analysis. Finally, drug susceptibility and degradation assays performed in mycobacteria demonstrate cellular activity of BacPROTACs, enabling conditional knockdowns of endogenous bacterial proteins fused to a developed degron. BacPROTAC technology represents a versatile research tool allowing the inducible degradation of bacterial proteins and paves the way to a novel antibiotic development modality.