Strength, ductility and toughness are key attributes of precipitate strengthened alloys, but remain challenging to achieve in many metallic systems. A detailed understanding of dislocation dynamics at precipitates is necessary for controlling work hardening, localized plasticity, plastic reversibility (e.g. Bauschinger effect), fatigue and failure, as well as the development of high performance steels, lightweight alloys, and high-temperature superalloys. Progress in these areas has been hampered by the lack of direct experimental evidence of detailed deformation mechanisms at precipitates, which prevents the verification and calibration of physics-based predictive computational models. Here, we use bimetallic core-shell nanocubes as model systems in which single precipitates (core nanocrystal) are isolated, and colloidal chemistry is used to tailor precipitate size, composition and defect structure. Nanocrystals are compressed using in-situ scanning electron microscope to obtain stress-strain behavior at individual precipitates, and characterized before and after compression using transmission electron microscopy. Molecular dynamics and discrete dislocation dynamics simulations are compared to experiments in order to determine the dislocation mechanisms responsible for the mechanical response. Here, we compare the mechanical behavior at semi-coherent precipitates in Au@Cu core-shell nanocubes and coherent precipitates in Au@Ag nanocubes. Au@Cu nanocubes have misfit dislocations at the core-shell interface and threading dislocations within the Cu shell, while Au@Ag nanocubes are defect-free. Au@Cu core-shell nanocubes are found to have higher strength, and strain hardening that is absent in Ag and Au@Ag nanocubes. We determine that deformation in Au@Cu nanocubes is governed by the motion of threading dislocations that extend from the bimetallic interface to the nanocube surface, that operate as single-arm sources. Plastic deformation in Au@Ag nanocubes occurs through the nucleation of dislocations at free surfaces.