Ionic surfactants such as sodium dodecyl sulfate (SDS) unfold proteins in a much more diverse yet effective way than chemical denaturants such as guanidium chloride (GdmCl). But how these unfolding processes compare on a molecular level is poorly understood. Here, we address this question by scrutinising the unfolding pathway of the globular protein S6 in SDS and GdmCl with single-molecule Forster resonance energy transfer (smFRET) spectroscopy. We show that the unfolding mechanism in SDS is strikingly different and convoluted in comparison to denaturation in GdmCl. In contrast to the reversible two-state unfolding behaviour in GdmCl characterised by kinetics on the timescale of seconds, SDS demonstrated not one, but four distinct regimes of interactions with S6, dependent on the surfactant concentration. At 50 mM SDS, the protein unfolds with millisecond timescale dynamics. We propose a detailed model for multi-stage unfolding of S6 in SDS, which involves at least three different types of denatured states with different level of compactness and dynamics and a continually changing landscape of interactions between protein and surfactant. Our results highlight the great potential of single-molecule fluorescence as a direct probe of nanoscale protein structure and dynamics in chemically complex surfactant environments.