A simple, low-cost, and reliable strategy was developed to prepare SERS substrates with ultra-high sensitivity using laser-induced selective metallization of polymers combined with an improved galvanic replacement reaction. To verify the SERS activity, organic analytes, such as Rhodamine 6G (R6G), crystal violet (CV), and methylene blue (MB), were selected as the probe molecules. Surprisingly, the detection limit of R6G reached as low as 1 × 10 −17 M in SERS tests with the excitation wavelength of 532 nm, which was superior to the data reported in most literature, indicating an ultra-high SERS sensitivity. XPS, WAXD, SEM, and EDS revealed that evenly distributed nanoparticles with 203 nm based on the Cu-Ag alloy were successfully formed on the Cu layer of the polymer. Besides, the RSD values of the main characteristic peaks of R6G were less than 0.20, showing a good reproducibility of the prepared SERS substrate. This SERS substrate also demonstrated good stability because it still kept a high SERS sensitivity after 35 days of air storage. Moreover, this new substrate showed the potential for reuse and probably addressed the problem that the traditional SERS substrate can only be used once. We believe this facile and reliable approach to preparing a new SERS substrate will have prospects for large-scale production and applications in the field of analytics.