A-site deficient perovskites are among the most important n-type thermoelectric oxides. Ceramics of Sr1−xPr2x/3□x/3TiO3 (x = 0.1–1.0) were prepared by solid-state reaction at 1700–1723 K using highly reducing atmospheres. Samples with the highest Sr content had a cubic crystal structure ; incorporating Pr with A-site vacancies led to a reduction in symmetry to tetragonal (I4/mcm) and then orthorhombic (Cmmm) crystal structures. HRTEM showed Pr2/3TiO3 had a layered structure with alternating fully and partially occupied A-sites and a short-range order along the (100) direction. Electrical conductivity was highest in samples of high symmetry (x ≤ 0.40), where the microstructures featured core-shell and domain structures. This enabled a very high power factor of approximately 1.75 × 10−3 W m−1 K−2 at 425 K. By contrast, at high Pr content, structural distortion led to reduced electron transport; enhanced phonon scattering (from mass contrast, local strain and cation–vacancy ordering) led to reduced, glass-like, thermal conductivity. Carbon burial sintering increased the oxygen deficiency leading to increased carrier concentration, a maximum power factor of approximately 1.80 × 10−3 W m−1 K−2 at 350 K and thermoelectric figure of merit of 0.26 at 865 K. The paper demonstrates the importance of controlling both crystal structure and microstructure to enhance thermoelectric performance.This article is part of a discussion meeting issue ‘Energy materials for a low carbon future’.