Quantum interference effects, as a distinctive feature of molecular devices, play an important role in regulating charge transport, thereby providing support for the design of devices with high switching ratios and high thermoelectric figures of merit. Therefore, in this work, we investigate the thermoelectric transport properties of extended linear conjugated molecular junctions using first-principles calculations combined with the non-equilibrium Green’s function (NEGF) method. Multiple connection sites are considered at both ends of the acene in the central molecular region, as well as at the molecular termini and their connections with the anchoring atoms. The transmission function and molecular projected self-consistent Hamiltonian (MPSH) eigenstates of each device are calculated. When electrons are injected from the A(B) sublattice and collected at the A(B) sublattice, destructive interference occurs near the Fermi energy. In contrast, when electrons are injected from the A(B) sublattice and collected at the B(A) sublattice, it results in constructive interference. This demonstrates that, in extended linear conjugated molecular systems, the quantum interference characteristics can be effectively predicted solely based on whether the sub-lattice properties of the two terminal connection sites are identical. In addition, by varying the molecular length of acene, it is found that quantum interference effects weaken the length dependence of the electrical conductance. As the molecular length increases, the conductance does not exhibit a significant change. This behavior is in stark contrast to the exponential decay of conductance with length typically observed in molecular wires under coherent tunneling transport. Meanwhile, as the molecular length increases, the HOMO and LUMO resonance peaks shift toward the Fermi level by approximately 0.45 eV and 1.14 eV, respectively. The transmission function of the p-M-p(aa) molecular junction exhibits a more pronounced antiresonance feature, resulting in a significant increase in the Seebeck coefficient. When the energy approaches −0.01 eV, the Seebeck coefficient of the p-Hep-p(aa) configuration reaches a maximum value of 401 μV/K. Through the synergistic modulation of these two factors, the maximum ZT values of the p-Hep-p(aa)-based molecular junction reaches nearly 8.