The quaternary AgPb18SbTe20 compound (abbreviated as LAST) is a prominent thermoelectric material with good performance. Endotaxially embedded nanoscale Ag-rich precipitates contribute significantly to decreased lattice thermal conductivity (κlatt) in LAST alloys. In this work, Ag in LAST alloys was completely replaced by the more economically available Cu. Herein, we conscientiously investigated the different routes of synthesizing CuPb18SbTe20 after vacuum-sealed-tube melt processing, including (i) slow cooling of the melt, (ii) quenching and annealing, and consolidation by (iii) spark plasma sintering (SPS) and also (iv) by the state-of-the-art flash SPS. Irrespective of the method of synthesis, the electrical (σ) and thermal (κtot) conductivities of the CuPb18SbTe20 samples were akin to those of LAST alloys. Both the flash-SPSed and slow-cooled CuPb18SbTe20 samples with nanoscale dislocations and Cu-rich nanoprecipitates exhibited an ultralow κlatt ∼ 0.58 W/m·K at 723 K, comparable with that of its Ag counterpart, regardless of the differences in the size of the precipitates, type of precipitate-matrix interfaces, and other nanoscopic architectures. The sample processed by flash SPS manifested higher figure of merit ( zT ∼ 0.9 at 723 K) because of better optimization and a trade-off between the transport properties by decreasing the carrier concentration and κlatt without degrading the carrier mobility. In spite of their comparable σ and κtot, zT of the Cu samples is low compared to that of the Ag samples because of their contrasting thermopower values. First-principles calculations attribute this variation in the Seebeck coefficient to dwindling of the energy gap (from 0.1 to 0.02 eV) between the valence and conduction bands in MPb18SbTe20 (M = Cu or Ag) when Cu replaces Ag.