DNA-encoded chemical libraries (DELs) are a cost-effective technology for the discovery of novel chemical probes and drug candidates. A major limiting factor in assembling productive DELs is the availability of DNA-compatible chemical reactions in aqueous media. In an effort to increase the chemical accessibility and structural diversity of small molecules displayed by DELs, we developed a robust Suzuki-Miyaura reaction protocol that is compatible with the DNA structures. By employing a water-soluble Pd-precatalyst, we developed conditions that allow efficient coupling of DNA-linked aryl halides with a wide variety of boronic acids/esters including heteroaryl boronates.