Anaerobic membrane bioreactor (AnMBR) technology is gaining interest for circular economy integration in the water sector. However, its complexity, arising from the integration of anaerobic processes with membrane technology, poses a key challenge. Developing an appropriate instrumentation, control, and automation (ICA) system is essential for its reliable long-term operation. In this study, an ICA system was developed to successfully manage an AnMBR pilot plant co-digesting two waste streams (microalgae and primary sludge). The ICA implementation enabled its stable long-term operation for 576 days, ensuring the proper performance of biological and filtration processes and yielding 215 NmLCH4·gCODinf−1 at 35 °C. Variables such as temperature, oxidation-reduction potential, permeate flux and biogas flow were identified as key parameters and controlled. This included a 23% reduction in the integral of absolute error compared to a PID controller for permeate flow and the maintenance of a 0.5% standard deviation for digester temperature. These controls enabled AnMBR performance optimization, the rapid detection of process issues, and early corrective actions. As a start-up strategy to ensure proper filtration performance in the long term, critical flux tests were conducted, guaranteeing a competitive total annualized equivalent cost of 0.0016 EUR/m3 for optimal conditions. The study also calculated greenhouse gas emissions in different scenarios, proposing optimal and more sustainable pilot plant operations, mesophilic conditions, biogas upgrading through microalgae cultivation, and grid injection, reducing emissions by 423 kgCO2e·tCOD−1. To ensure the viability of emerging technologies such as AnMBR, proper start-up protocols are crucial, including favorable filtration and biological process operating conditions, ICA implementation, and key parameter control for technical, economic and environmental success.