Current routes for synthesizing antibody-drug conjugates commonly rely on maleimide linkers to react with cysteine thiols. However, thioether exchange with metabolites and serum proteins can compromise conjugate stability and diminish in vivo efficacy. We report the application of a phenyloxadiazole sulfone linker for the preparation of trastuzumab conjugates. This sulfone linker site-specifically labeled engineered cysteine residues in THIOMABs and improved antibody conjugate stability in human plasma at sites previously shown to be labile for maleimide conjugates. Similarly, sulfone conjugation with selenocysteine in an anti-ROR1 scFv-Fc improved human plasma stability relative to maleimide conjugation. Kinetically controlled labeling of a THIOMAB containing two cysteine substitutions was also achieved, offering a strategy for producing antibody conjugates with expanded valency.