Despite multifunctional theranostics hold vast potential in deep tissue bioimaging and tumor therapy, activatable nanomedicine with integration of precise diagnosis and effective treatment is usually achieved at the cost of complicated synthesis chemistries. Here, a facile way to design bioresponsive Ag2S‐Ag Janus probes coated by polyethylene glycol (PEG) (denoted as AAP) is showed, active in the second near‐infrared window (NIR‐II, 1000–1700 nm). In tumor microenvironment, Ag part can yield hydroxyl radicals (·OH) by consuming H2O2 for high‐efficiency chemodynamic therapy (CDT), while Ag2S part has impressive photothermal therapy (PTT). The synergistic benefits from Ag and Ag2S parts further boosted CDT effect of AAP Janus probes with high photothermal conversion efficiency up to 56.8%. Moreover, multiple lines of evidence supported that extremely faint fluorescence of AAP Janus probes can be significantly activated by overexpressed levels of H2O2, showing bright NIR‐II emission at ≈1270 nm with over 5.6 × 103‐fold increase in signal intensity. AAP Janus probes are easily activatable for NIR‐II imaging for tumor‐specific identification, and effectively ablate tumor tissues with tumor inhibition rate of 96.2%. This study expects that AAP Janus probe will open up a new route to achieve precise tumor diagnosis and treatment in the NIR‐II window.