Abstract We report on the facile synthesis of anatase multi-doped TiO2 mesocrystals with highly energetic {001} facets and their outstanding photocatalytic activity. The structural and compositional properties were investigated via different techniques such as XRD, XPS, Raman photoluminescence, and electron paramagnetic resonance, which confirmed the fabrication of C, Co, and Ti3+-doped anatase single crystal-like mesocrystals. The Mott-Schottky analysis showed a drastic increase in the carrier density upon cobalt doping, resulting in a 6-fold increase in the photoelectrochemical performance compared to the undoped sample. Besides, the photocatalytic efficiency of the as-fabricated mesocrystals in the photochemical production of hydrogen was estimated under AM1.5 conditions without using any hole scavengers. The Co-doped C/Ti3+ TiO2 mesocrystals showed an unprecedented hydrogen production rate when compared to the other similar titanium-based mesocrystals. Finally, the unprecedented enhancement of Co-doped C/Ti3+ TiO2 mesocrystals in water splitting makes them promising candidates for various photocatalytic applications.