Inhibition of β-lactamases is a promising strategy to overcome antimicrobial resistance to commonly used β-lactam antibiotics. Boronic acid derivatives have proven to be effective inhibitors of β-lactamases due to their direct interaction with the catalytic site of these enzymes. We synthesized a series of phenylboronic acid derivatives and evaluated their structure-activity relationships as Klebsiella pneumoniae carbapenemase (KPC-2) inhibitors. We identified potent KPC-2 inhibitors 2e & 6c (Ki = 0.032 μM and 0.038 μM, respectively) that enhance the activity of cefotaxime in KPC-2 expressing Escherichia coli. The measured acid dissociation constants (pKa) of selected triazole-containing phenylboronic acids was broad (5.98–10.0), suggesting that this is an additional property of the compounds that could be tuned to optimize the target interaction and/or the physicochemical properties of the compounds. These findings will help to guide the future development of boronic acid compounds as inhibitors of KPC-2 and other target proteins.