The formation of brittle intermetallic compounds (IMCs) at the interface during Al–Ni dissimilar joining deteriorates joint strength, thereby limiting their applicability in high-performance engineering structures. This study investigates the effects of a high-entropy alloy (HEA) interlayer, CoCrFeMnNi, and post weld heat treatment (PWHT) on the interfacial microstructure and mechanical performance in dissimilar Al–Ni friction stir lap welding (FSLW). Without the interlayer, a brittle Al3Ni IMC layer formed at the interface and grew significantly after PWHT, leading to interfacial fracture and reduced joint efficiency (∼20 %). In contrast, the application of an HEA interlayer suppressed IMC formation and led to the formation of a nanoscale amorphous layer under as-welded conditions, which effectively prevented interfacial fracture and enhanced joint efficiency (∼63 %). After PWHT, a favourable Al13M4 IMC layer formed, wherein the M-site was co-occupied by Co, Cr, Fe, Mn, and Ni. This IMC exhibited no brittleness and effectively prevented interfacial fracture. Moreover, superior joint strength was achieved after PWHT which promoted the re-precipitation of strengthening precipitates that had previously been dissolved during FSLW owing to thermal exposure of the Al matrix. Joint efficiency thus improved to ∼93 % which is comparable to the base metal. The synergistic combination of an HEA interlayer and PWHT is a promising strategy for suppressing the formation and growth of brittle IMCs and for enhancing the reliability of dissimilar Al–Ni joints.