Cases of travel-associated Legionnaires' disease (TALD) are frequently reported in Italy. From 1987 to 2021, 61 cases of TALD were linked to 22 hotels in a municipality in northern Italy. Legionella pneumophila serogroup 1 (Lp1) strains isolated from both patients and hotel water systems were identified as sequence type (ST) 901, a genotype rarely associated with travel-related infections in Italy or elsewhere. Whole-genome sequencing was used to analyze 41 isolates, and phylogenetic relationships were inferred by core genome multilocus sequence typing (cgMLST), single nucleotide polymorphisms (SNP) and pangenome analyses. The Lp ST901 isolates were found to form a clade characterized by some accessory genomic islands (AGI) already described in other epidemic strains, such as Alcoy, Corby, Paris and Philadelphia; other islands, containing either transposase/recombinase or transcriptional regulator factors or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-cas systems, were specific to Lp ST901. Lp ST901 also appears to have undergone possible recombination with other strains, such as Lp ST47 (Lorraine strain). Additionally, CRISPR-Cas systems may have contributed to the protection of Lp ST901 from external dangers, while the colonized hotel water systems may have provided an ideal environmental protective niche. Our findings highlight that Lp ST901 has public health significance and deserves attention in Legionnaires' disease surveillance and risk assessment.