Near-infrared (NIR) emitting fluorophores are powerful tools for optical imaging. However, there are only a handful of broadly employed NIR-emitting scaffolds, and the synthetic methods to prepare these molecules are often problematic. Here, we describe a novel, three-step synthesis of chromene-containing hemicyanine probes exhibiting large Stokes shifts and NIR emissions. We develop a pH-activatable probe for visualizing lysosomal trafficking of mAb conjugates. These studies provide a concise approach to hemicyanines with promising properties.