ο-Nitrobenzyl (ONB) derivatives are one of the most investigated photo-responsive functional group that features irreversible photolysis under a light stimulus. They are easy to synthesize and display excellent photoactivity, thus have been widely used to construct photo-responsive polymers for numerous applications, such as controlled drug delivery, photodegradable materials, photoinduced micropatterns, etc. This review article is focused on ONB derivatives and their developments in polymer science. The article provides an up-to-date information, including photolysis mechanism, structural design, and materials properties, with a special focus on the application development of ONB derivatives in different areas of polymer science. In addition, the challenges and outlook based on our understanding are also provided. We believe this article will be of interest to the readers from both scientific and industrial communities and will help the readers understand the latest developments in the field, thereby enlightening thoughts for the design of photo-responsive polymers.