Rhodamine dyes have been extensively explored for bioimaging and therapeutic applications over the past few decades. However, it remains a challenge to design long‐wavelength and large Stokes shift rhodamine derivatives to meet the requirements of fluorescence imaging and phototherapy in deep living tissues. In this work, a pyridine aromatic unit was inserted into the ACF skeleton to prepare a series of stable rhodamine derivatives, ACFPs, to achieve long emission wavelength (> 650 nm) and large Stokes shift (~ 60 nm) by tuning the conjugated systems and electronic symmetry. More significantly, ACFPs are capable of continuously producing superoxide radical (O2‐•) under long wavelength irradiation. This study presents a novel paradigm for improving the optical properties of rhodamine, which has led to the development of a novel tool for image‐guided phototherapy for cancer treatment.