Quantitative microstructural studies using optical and electron microscopy were carried out to determine the grain size and intermetallic particle distributions in various locations of friction stir welds in AA5251 to study their influence on the microhardness. Grain-boundary strengthening, (using Hall-Petch relation) was found to be the dominant factor controlling weld hardness within the thermomechanically-affected zone (TMAZ), yet with a minor increase in the Hall-Petch intercept from the Al-Mg alloys literature values. This deviation was associated with solid-solution strengthening resulting from the dissolution of Mg2Si particles during welding. A contribution from precipitate strengthening accounted for deviations from the overall Hall-Petch relationship. This was linked to the formation of submicron Al-6(Fe,Mn) particles observed within the TMAZ grains, varying in density with position in the weld, and accordingly their strength contribution. Differential Scanning Calorimetry (DSC) was used to quantify the strengthening contribution of the dislocation stored energy in the TMAZ of the weld. Although significant stored energy was detected, this was mostly due to the presence of geometrically-necessary (non-strengthening) dislocations and did not contribute to hardness.