Lead sulfide (PbS) has emerged as a cost-effective and thermally stable alternative to PbTe and PbSe for mid-temperature thermoelectric applications. However, conventional heavy elemental doping strategies often compromise the power factor near 300 K attributed to the enhanced ionized impurity scattering. Herein, we report a synergistic approach to improve the ZT value of n-type PbS by trace InSb doping and Cu dynamic doping. The introduction of trace InSb simultaneously optimizes carrier concentration and effective mass while mitigating mobility loss, resulting in a remarkable enhancement in average power factor from ∼9.43 μW cm −1 K −2 to ∼16.32 μW cm −1 K −2 over 300–773 K. Meanwhile, a marked reduction in lattice thermal conductivity was observed, stemming from intensified phonon scattering caused by In/Sb interstitials. Further Cu doping dynamically regulates carrier concentration as temperature increases, yielding a near threefold surge in carrier mobility at 300 K from ∼166 cm 2 V −1 s −1 to ∼393 cm 2 V −1 s −1 . As a result, Pb 0.99875 (InSb) 0.00125 S+2.0 %Cu achieves a peak ZT value of ∼1.1 and a competitive average ZT value of ∼0.65 across 300–773 K, surpassing most reported n-type PbS-based materials. Ultimately, a single-leg power generation efficiency of 4.1 % was achieved under a temperature difference of 500 K. This study demonstrates a promising route to decouple interrelated thermoelectric parameters and advance PbS-based systems for efficient power generation and thermoelectric cooling applications. • The thermoelectric properties of n-type PbS are enhanced by regulating the energy band structures and dynamic doping. • Increasing the average power factor from ∼9.43 μW cm −1 K −2 to ∼16.32 μW cm −1 K −2 through trace InSb doping. • Improving the carrier mobility from ∼166 cm 2 V −1 s −1 to ∼393 cm 2 V −1 s −1 via Cu dynamic doping. • Achieving a high average ZT value of ∼0.65 and a competitive conversion efficiency of 4.1 %.