We report the demonstration of a low-power pixelated readout system designed for three-dimensional ionization charge detection and digital readout of liquid argon time projection chambers (LArTPCs) . Unambiguous 3D charge readout was achieved using a custom-designed system-on-a-chip ASIC (LArPix) to uniquely instrument each pad in a pixelated array of charge-collection pads. The LArPix ASIC, manufactured in 180 nm bulk CMOS, provides 32 channels of charge-sensitive amplification with self-triggered digitization and multiplexed readout at temperatures from 80 K to 300 K . Using an 832-channel LArPix-based readout system with 3 mm spacing between pads, we demonstrated low-noise (0<50 e− RMS equivalent noise charge) and very low-power (<100 μW/channel) ionization signal detection and readout . The readout was used to successfully measure the three-dimensional ionization distributions of cosmic rays passing through a LArTPC, free from the ambiguities of existing projective techniques. The system design relies on standard printed circuit board manufacturing techniques, enabling scalable and low-cost production of large-area readout systems using common commercial facilities. This demonstration overcomes a critical technical obstacle for operation of LArTPCs in high-occupancy environments, such as the near detector site of the Deep Underground Neutrino Experiment (DUNE) .