Near-infrared (NIR) in vivo fluorescence imaging has exhibited the distinct advantage of high optical resolution at deeper penetration into biological tissues. AgTe quantum dots (QDs), with a relatively narrow band gap, show great promise for fluorescence emission at long wavelengths in the second near-infrared (NIR-II) window for bioimaging. However, existing AgTe QDs have severely hindered the application of in vivo bioimaging due to their poor fluorescence brightness and stability, so it is important to prepare AgTe QDs with high quantum yield and stability as well as high biocompatibility in the NIR-II window. Herein, we designed an integrated method for the preparation of water-soluble AgTe QDs by mutual adaptation of QD synthesis and surface modification. We first synthesized high-quality AgTe QDs with different NIR-II emission wavelengths and the photoluminescence quantum yields (PLQYs) up to 6.51% by rapidly injecting the TBP-Te precursor into a hot solvent to form a highly fluorescent AgTe core. Then water-dispersible AgTe QDs were obtained by direct exchange of the hydrophobic AgTe QD surface ligands with thiol ligands. The PLQY of the water-soluble AgTe QDs obtained by this method can still be maintained at 4.94%. With these highly bright and stable AgTe QDs, the abdominal vessels, hindlimb arterial vessels, venous vessels, sacral lymph nodes, and tumor vessels were visualized non-invasively in vivo in the NIR-II window in mice. The results demonstrate that the integrated strategy of QD synthesis and modification provides valuable technical support for further in-depth applications of AgTe QDs.