<p>While oceanic and coastal acidification has gained increased attention, long-term pH trends and their drivers in large freshwater systems remain poorly understood. The Laurentian Great Lakes are the world’s largest freshwater system, and in many ways resemble marine ecosystems. However, unlike the open ocean and coastal waters where pH has declined due to rising atmospheric CO₂, no significant pH trends have been observed in the Laurentian Great Lakes, despite significant ecosystem changes driven partly by the invasion of dreissenid mussels. This study examined 41 years of field observations from Lake Michigan to investigate the long-term carbonate chemistry dynamics. Observational results revealed substantial declines in both total alkalinity (TA) and dissolved inorganic carbon (DIC) over the four decades. Mussel shell calcification emerged as the primary mechanism behind these declines, accounting for 97% and 47% of the observed changes in TA and DIC, respectively, lowering water column pH by 0.24 units. Elevated carbon accumulation in soft mussel tissues, coupled with long-term changes in the air-water <i>p</i>CO₂ gradient during summer, significantly contributed to long-term DIC variations, explaining 18% and 28% of the lake-wide DIC loss. These two mechanisms also resulted in an overall pH increase of 0.09 and 0.12 units, largely offsetting the calcification-driven pH decrease. These findings bridge a gap in acidification research for large freshwater systems and provide valuable insights for comprehensive lake-wide management strategies.</p>