Successful establishment of non‐native species is strongly influenced, among other factors, by the genetic variation of founding populations, which can be enhanced by multiple introductions through admixture. Coexisting pathogens can also facilitate the establishment of non‐native species by detrimentally impacting on the native fauna acting as novel weapons. The signal crayfish (Pacifastacus leniusculus) is a highly invasive species, which has caused mass declines of native crayfish in Europe through displacement and transmission of the oomycete Aphanomyces astaci (crayfish plague), which is typically lethal to native European crayfish. However, whether Aphanomyces astaci may have facilitated the invasion of the signal crayfish is not known. We estimated the genetic diversity at microsatellite DNA loci, effective population size, and potential origins of seven infected and noninfected signal crayfish populations in Europe and one founder population in North America. Approximate Bayesian computation analysis and population structuring suggested multiple host introductions from diverse source populations, as well as higher heterozygosity among infected than uninfected populations, which could reflect a fitness advantage. Low effective population size, moderate heterozygosity, and lack of isolation by distance suggest that some invasive signal crayfish populations may not be fully established or that their genetic diversity may have been reduced by eradication attempts.