The harsh truth is: microplastics (MPs) are everywhere. These micro-sized polymers are ubiquitously distributed throughout all environmental and urban aquatic pathways. In the last decade, microalgae have been attracting increasing attention as a unique biomass feedstock for biofuel production, representing a sustainable and pollution-free fuel spring that is obtained from renewable sources. Recent reports have documented that wastewater treatment plants, central to urban water distribution to industries, discharge a median value of 2 million MPs/day. Given that water quality is a critical parameter in microalgal-based industries, the microalga Phaeodactylum tricornutum was grown in medium contaminated with environmental- and industrial-relevant (0.5 and 50 mg/L) concentrations of polystyrene and/or polymethyl methacrylate. Biochemical parameters such as cell growth, pH, biomass, photosynthetic pigments, extracellular carbohydrates and proteins were assessed over the microalgal full growth cycle (27 days). Overall, a two-stage response was observed, with a polymer- and concentration-specific growth enhancement occurring in an early exponential phase, followed by an adaptive response that lead to a recovery until the stationary phase was reached. Results show that the production of photosynthetic pigments was pH-correlated during the first-stage response, while exhibiting a cell density-independent biochemical regulation in later stages of culturing. The biosynthesis of extracellular carbohydrates also followed the two-stage response, with emphasis on the major decrease exhibited during long-term exposure to MPs. Astonishingly, despite the long-term exposure to MPs not affecting cell abundance all across, a severe decrease in biomass yield (of up to 82%) was observed at the end of the culturing period. Altogether, this pilot laboratory-scale study shows that microalgal exposure to MPs disturbs its biochemical equilibrium, in a time-dependent manner, decreasing economically valuable biomass production. These results indicate that an “invisible”, but highly abundant and ubiquitous pollution source in water might be playing an important role in the viability of microalgal-biomass biotechnology industry.