Aggregation of human islet amyloid polypeptide (hIAPP, amylin) into amyloid fibrils is a hallmark of β-cell dysfunction in type 2 diabetes, yet the molecular determinants governing its aggregation pathways remain incompletely understood. Here, we investigate how systematic fluorination of Phe23─a key aromatic residue within the amyloidogenic core─modulates intra- and intermolecular interactions and thereby probes hIAPP self-assembly under physiologically relevant acidic and neutral pH conditions. Using a combination of Thioflavin T kinetics, scaling-exponent analysis, pyrene fluorescence, ion mobility–mass spectrometry, circular dichroism, 19F NMR spectroscopy, and molecular dynamics simulations, we show that fluorination of Phe23 reshapes aggregation behavior in a highly nonadditive manner. While wild-type and minimally fluorinated variants, at neutral pH, follow the surface-catalyzed secondary nucleation mechanism discussed well in the literature, higher degrees of fluorination progressively reduce monomer dependence and give rise to pronounced concentration-dependent, self-inhibiting aggregation behavior. Under acidic conditions, protonation of His18 leads to a divergent concentration dependence, with reduced monomer dependence for wild-type and minimally fluorinated peptides and enhanced concentration sensitivity for tetra- and penta-fluorinated variants. These concentration dependencies reflect differences in the conformational accessibility, flexibility, and oligomerization efficiency required for productive fibril formation under each pH condition. Together, these results identify Phe23 as a molecular switch that couples local interactions to global aggregation pathways and demonstrate how subtle chemical and environmental perturbations can modulate the productivity of hIAPP fibril formation.