Transient interactions in which binding partners retain significant conformational disorder play an essential role in regulating the dynamics and specificity of biological networks, challenging the expectation that specificity demands structurally defined and unambiguous molecular interactions. The dynamic and transient nature of these so-called ‘fuzzy’ interactions render them challenging to characterize experimentally, so the mechanisms by which specificity can arise from fuzzy interactions remain unclear. We recently identified fuzzy interactions in the unusual context of the strain-specific recognition of a conserved epitope of the malaria antigen, merozoite surface protein 2 (MSP2).1 MSP2 is intrinsically disordered and is an important malaria vaccine candidate. The monoclonal antibody 6D8 recognizes a conserved continuous 9-residue epitope within the N-terminal region of MSP2, yet it has different affinities for the different allelic forms of MSP2. This unexpected strain-specificity is caused by fuzzy interactions involving polymorphic residues immediately C-terminal to the structurally defined epitope. NMR chemical shift perturbations and paramagnetic relaxation enhancements indicate that these interactions are distributed across a broad region of the 6D8 surface surrounding the crystallographically-defined antigen binding site, and are largely sequence independent. Relaxation data confirm the transient nature of these interactions and highlight subtle differences in their extent or timescale that contribute to the observed specificity. These experimental data are integrated with molecular dynamics simulations, yielding a coherent picture in which the polymorphic C-terminal extension engages in multiple transient and largely sequence-independent interactions distributed across much of the accessible antibody surface. Thus, specificity in this system arises as a consequence of subtle differences in what are essentially non-specific interactions.