Persistent luminescence without excitation light and tissue autofluorescence interference holds great promise for biological applications, but is limited by available materials with long‐wavelength emission and excellent clinical potential. Here, we report that porphyrin derivatives can emit near‐infrared persistent luminescence over 60 min after cessation of excitation light or on interaction with peroxynitrite. A plausible mechanism of the successive oxidation of vinylene bonds was demonstrated. A supramolecular probe with a β‐sheet structure was constructed to enhance the tumor targeting ability and the photoacoustic and persistent luminescence signals. Such probes featuring light‐triggered function transformation from photoacoustic imaging to persistent luminescence imaging permit advanced image‐guided cancer surgery. Furthermore, peroxynitrite‐activated persistent luminescence of the supramolecular probe also enables rapid and precise screening of immunogenic cell death drugs. Porphyrin derivatives that can emit near‐infrared persistent luminescence (PL) over 60 min are reported and a mechanism for the phenomenon is proposed. The derivatives are used to synthesize supramolecular probes with peroxynitrite‐activated PL and light‐triggered imaging‐modality transformation characteristics that permit improved biological uses.