There is growing interest in the development of chemiluminescence (CL) probes for phototheranostics because of their minimized tissue autofluorescence. However, due to a lack of near‐infrared (NIR)‐absorbing chemiluminophores, current probes for NIR CL‐guided phototherapy are based on nanoparticles made up of multiple components. We report bright unimolecular chemiluminophores with NIR absorptions and emissions, long CL half‐lives and ideal photodynamic efficiency. One luminophore is modified into an activatable probe, DBPOL, with a turn‐on CL signal and photodynamic activity that are specific to a cancer biomarker. The highly sensitive DBPOL allows CL‐guided photodynamic therapy which completely inhibits tumor growth and lung metastasis in mouse models, and can be applied for noninvasive monitoring of lung metastasis. We provide molecular guidelines for NIR‐absorbing CL probes for imaging‐guided phototherapy.