Multi-electrode array (MEA) recordings are widely utilized to characterize neuronal network activity. However, currently each manufacturer distributes proprietary software that operates exclusively on its own file format. Since no cross-platform, open-source pipeline currently exists. Thus, we created CASCADE (Criticality Avalanche Spike Cross-platform Analysis Detection Engine), a Python-based command-line (bash) pipeline to analyze MEA recordings from 3Brain, Axion Biosystems, Cortical Labs, Maxwell Biosystems, and Multi-Channel Systems MEA devices. CASCADE measures the standard parameters such as: network, burst, firing rate frequency, and also measures criticality and avalanches. CASCADE criticality calculation was benchmarked across six MEA recordings from five manufacturers, resulting in comparable values because all recordings were analyzed using identical computational methods regardless of manufacturer file format. Thus, CASCADE provides a flexible and robust MEA analysis pipeline that can also analyze neuronal avalanches and criticality from multiple MEA devices from different manufacturers.