We combine molecular dynamics simulations and new high-field NMR experiments to describe the solution structure of the Aβ_21–30 peptide fragment that may be relevant for understanding structural mechanisms related to Alzheimer’s disease. By using two different empirical force-field combinations, we provide predictions of the three-bond scalar coupling constants (³J_H^NH^α), chemical-shift values, ¹³C relaxation parameters, and rotating-frame nuclear Overhauser effect spectroscopy (ROESY) crosspeaks that can then be compared directly to the same observables measured in the corresponding NMR experiment of Aβ_21–30. We find robust prediction of the ¹³C relaxation parameters and medium-range ROESY crosspeaks by using new generation TIP4P-Ew water and Amber ff99SB protein force fields, in which the NMR validates that the simulation yields both a structurally and dynamically correct ensemble over the entire Aβ_21–30 peptide. Analysis of the simulated ensemble shows that all medium-range ROE restraints are not satisfied simultaneously and demonstrates the structural diversity of the Aβ_21–30 conformations more completely than when determined from the experimental medium-range ROE restraints alone. We find that the structural ensemble of the Aβ_21–30 peptide involves a majority population (~60%) of unstructured conformers, lacking any secondary structure or persistent hydrogen-bonding networks. However, the remaining minority population contains a substantial percentage of conformers with a β-turn centered at Val24 and Gly25, as well as evidence of the Asp23 to Lys28 salt bridge important to the fibril structure. This study sets the stage for robust theoretical work on Aβ_1–40 and Aβ_1–42, for which collection of detailed NMR data on the monomer will be more challenging because of aggregation and fibril formation on experimental timescales at physiological conditions. In addition, we believe that the interplay of modern molecular simulation and high-quality NMR experiments has reached a fruitful stage for characterizing structural ensembles of disordered peptides and proteins in general.