The mechanical behaviour at room temperature of a single-crystal superalloy exposed to long-term ageing at elevated temperature has been investigated, a topic important for the material’s resistance to thermal–mechanical fatigue. Specimens with several different crystallographic orientations were plastically deformed in either tension or compression before and after the long-term furnace exposure. While the thermally activated degradation of the microstructure causes a reduction in yield limit of up to 25% for specimens initially deformed in the [001] and [011] directions, none or only moderate reduction was seen for specimens initially deformed along the [1¯11] direction. This can be explained by the strong correlation between yield limit reduction and the amount of γ′ coarsening. By introducing an isotropic degradation function in a newly developed crystal plasticity model, the constitutive behaviour of both virgin and degraded material has been described with good agreement with the experimental results.