Dissimilar metal welds (DMWs) are a key design feature in nuclear power systems, typically involving ferritic low-alloy steels (LAS), stainless steels (SS), and nickel-base alloys. They are, however, a potential concern regarding the structural integrity of nuclear power systems. In particular, the LAS/nickel-base alloy weld metal interface is known to develop a local strength mismatch upon post-weld heat treatment (PWHT). Very limited data is available on the effect of thermal ageing on the DMW interface. The aim of this study was to investigate the effects of thermal ageing at 400 °C for up to 10,000 h on a narrow-gap DMW mock-up representative of the weld between the reactor pressure vessel nozzle and its safe-end after PWHT, with a special focus on the LAS SA 508/nickel-base Alloy 52 weld metal interface. No significant effect of thermal ageing on the appearing microstructure was observed in either LAS base material, LAS heat-affected zone or Alloy 52 weld metal. However, thermal ageing reduced the local strength mismatch at the LAS/nickel-base weld metal interface formed during PWHT. The reduction of the strength mismatch was detected using nanoindentation measurements and was concluded to be associated with a decrease in the carbon pile-up in the weld metal caused by PWHT. Based on the obtained results, thermal ageing promotes carbon diffusion from the weld metal side of the fusion boundary further away into the weld metal and thus slightly decreases the local strength mismatch.