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Interactions between transmembrane (TM) helices play a critical role in the fundamental processes required for cells to communicate and exchange materials with their surroundings. Our understanding of the factors that promote TM helix interactions has greatly benefited from our ability to study these interactions in the solution phase through the use of membrane-mimetic micelles. However, less is known about the potential influence of juxtamembrane regions flanking the interacting TM helices that may modulate dimerization affinities, even when the interacting surface itself is not altered. To investigate this question, we used solution NMR to quantitate the dimerization affinity of the major coat protein from the M13 bacteriophage in sodium dodecyl sulfate (SDS), a well-characterized model of a single-spanning self-associating TM protein. Here, we showed that a shorter construct lacking the N-terminal amphipathic helix has a higher dimerization affinity relative to that of the full-length protein, with no change in the helical structure between the monomeric and dimeric states in both cases. Although this translated into a 0.6 kcal/mol difference in free energy when the SDS solvent was approximated as a continuous phase, there were deviations from this model at high protein to detergent ratios. Instead, the equilibria were better fit to a model that treats the empty micelle as an active participant in the reaction, giving rise to standard free energies of association that were the same for both full-length and TM-segment constructs. According to this model, the higher apparent affinity of the shorter peptide could be completely explained by the enhanced detergent binding by the monomer relative to that bound by the dimer. Therefore, differential detergent binding between the monomeric and dimeric states provides a mechanism by which TM helix interactions can be modulated by noninteracting juxtamembrane regions.