Demand for large area parallel plate ionization chamber (PPIC) or large area ionization chamber (LAIC) has risen in recent years due to several advantages of the large effective area in monitoring therapeutic radiation beams. PPICs are designed for the measurements of beam profile and dosimetry in radiation therapy quality assurance (QA) procedures. Objective. Heterogeneous responses over the large sensitive area pose an undeniable concern for the straightforward applications of PPICs in clinical dosimetry. Uniformity calibration for the detector response is thus essential for the accurate performance of each PPIC unit. Approach. A large area XY strip PPIC, characterized by a large effective area of 345.44 × 345.44 mm2 and 256 readout channels, was investigated in this study. A new systematic uniformity calibration is developed to improve the lateral response of the PPIC over the measurements for both narrow beams and large square field beams. A 2D response map of the PPIC was obtained by a spot-scanning method using a compact x-ray tube (mini x-ray). The mini x-ray, providing stable radiation (uncertainty <0.1%), was moved with a step size of 20 mm in 2 dimensions across the entire PPIC surface to collect a complete spot scan. Different uniformity calibration methods were introduced for the measurement of the PPIC by adopting the information from the detector 2D response map. Main results. Deviation of the detector response, before calibration, was observed to reach about 7% for the testing PPIC unit which is much higher than the recommended uniformity response of 1% (IAEA TRS-398). The uniformity response of the PPIC improved significantly to less than 1% across the detector surface after calibration. Significance. The proposed methods enable the practical application of PPIC in routine clinical dosimetry and can be reliably adopted by any radiation facility to perform daily and monthly QA.