We report a new facile route for preparing surface-enhanced Raman scattering (SEAS) substrates with tailored enhancement mechanisms. Silver nanowires were assembled using the Langmuir-Blodgett (LB) technique and further processed via galvanic replacement reactions (GRRs). The GRRs provided an efficient method to decrease the spectral noise caused by the capping agent polyvinylpyrrolidone. A decrease in noise along with the addition of gold nanostructures to the system revealed Raman signals from nonfluorescent molecules associated with a charge-transfer mechanism. The GRR LB substrates exhibited ultrasensitive SERS ability with a detection limit as low as 8 nM using 4-aminothiophenol, partially due to the strong chemical binding between the SERS substrates and probe molecules. Furthermore, the GRRs provide a facile route in tailoring SERS substrates to target molecules in a controlled manner.