Coagulation is the most sensitive step in drinking water treatment. Underdosing may not yield the required water quality, whereas overdosing may result in higher costs and excess sludge. Traditionally, the coagulant dosage is set based on bath experiments performed manually. Therefore, this test does not allow real-time dosing control, and its accuracy is subject to operator experience. Alternatively, solutions based on machine-learning (ML) have been evaluated as a computer-aided alternative. Despite these advances, there is open debate on the most suitable ML method applied to the coagulation process, capable of the most highly accurate prediction. This study addresses this gap, where a comparative analysis between ML methods was performed. As a research hypothesis, a novel data-driven fuzzy inference system (FIS) should provide the best performance due to its ability to deal with uncertainties inherent to complex processes. Although ML methods have been widely investigated, only a few studies report hybrid neuro-fuzzy systems applied to coagulation. Thus, to the best of our knowledge, this is the first study thus far to address the accuracy of this novel data-driven FIS for such application. The novel FIS provided the smallest error (0.86), indicating a promising alternative tool for real-time and highly accurate coagulant dosing in drinking water treatment.