Water quality guarantee in remote areas necessitates the development of portable, sensitive, fast, cost-effective, and easyto-use water quality detection methods. The current work reports on a microfluidic paper-based analytical device (μPAD) integrated with a smartphone app for the simultaneous detection of cross-type water quality parameters including pH, Cu(II), Ni(II), Fe(III), and nitrite. The shapes, baking time, amount, and ratios of reaction reagent mixtures of wax μPAD were optimized to improve the color uniformity and intensity effectively. An easy-to-use smartphone app was established for recording, analyzing, and directly reading the colorimetric signals and target concentrations on μPAD. The results showed that under the optimum conditions, the current analytical platform has reached the detection limits of 0.4, 1.9, 2.9, and 1.1 ppm for nitrite, Cu(II), Ni(II), and Fe(III), respectively, and the liner ranges are 2.3−90 ppm (nitrite), 3.8−400 ppm (Cu(II)), 2.9−1000 ppm (Ni(II)), 2.8−500 ppm (Fe(III)), and 5−9 (pH). The proposed portable smartphone-app integrated μPAD detection system was successfully applied to real industrial wastewater and river water quality monitoring. The proposed method has great potential for field water quality detection.