Polymer waveguide devices have attracted increasing interest in several rapidly developing areas of broadband communications since they are easily adaptable to on-chip integration and promise low propagation losses. As a key member of the waveguide gain medium, lanthanide doped nanoparticles have been intensively studied to improve the downconversion luminescence. However, current research efforts are almost confined to erbium-doped nanoparticles and amplifiers operating at the C-band; boosting the downconversion luminescence of Tm3+ for S-band optical amplification still remains a challenge. Here we report a Tb3+-induced deactivation control to enhance Tm3+ downconversion luminescence in a stoichiometric Yb lattice without suffering from concentration quenching. We also demonstrate their potential application in an S-band waveguide amplifier and record a maximum optical gain of 18 dB at 1464 nm. Our findings provide valuable insights into the fundamental understanding of deactivation-controlled luminescence enhancement and open up a new avenue toward the development of an S-band polymer waveguide amplifier with high gain.