Ticks are hematophagous parasites that can transmit a variety of human pathogens, and their life cycle is dependent on several climatic factors for development and survival. We conducted a study in Piedmont and Aosta Valley, Italy, between 2009 and 2018. The study matched human sample serologies for Borrelia spp. with publicly available climatic and meteorological data. A total of 12,928 serological immunofluorescence assays (IFA) and Western blot (WB) tests were analysed. The median number of IFA and WB tests per year was 1236 (range 700-1997), with the highest demand in autumn 2018 (N = 289). In the study period, positive WB showed an increasing trend, peaking in 2018 for both IgM (N = 97) and IgG (N = 61). These results were consistent with a regional climatic variation trending towards an increase in both temperature and humidity. Our results suggest that coupling data from epidemiology and the environment, and the use of a one health approach, may provide a powerful tool in understanding disease transmission and strengthen collaboration between specialists in the era of climate instability.