Objective To analyze the epidemiological characteristics, changing trends, and spatial-temporal aggregation of hand-foot-mouth disease (HFMD) in Wenzhou from 2013 to 2022, so as to scientifically guide the decision-making of prevention and control. Methods The infectious disease report data for HFMD in Wenzhou city were collected from the China Disease Prevention and Control Information System for the period 2013—2022. Spatial-temporal scanning analysis was conducted using StatsCan software, and spatial autocorrelation analysis was performed using ArcMap 10.2 software to identify spatial-temporal aggregation patterns. Results A total of 260 401 cases of HFMD were reported in Wenzhou from 2013 to 2022, with an average annual incidence of 276.93 per 100 000 and a severe disease rate of 13.82 per 100 000. The incidence exhibited a decreasing trend (χ²_trend=26 402.606, P < 0.05). The incidence rate among individuals over 6 years old increased (χ²_trend=1 814.455, P < 0.05), as did the rates among nursery children, students, and teachers (χ²_trend=5 493.085, P < 0.05; χ²_trend=1 752.584, P < 0.05; χ²_trend=9.424, P < 0.05). Spatial analysis revealed aggregation of HFMD cases in 2017, with a Moran I value of 0.433 514 (Z=2.42 775 and P=0.015 193), indicating positive spatial correlation and hot spots concentrated in Wencheng county and Pingyang county. Spatial-temporal scanning identified a primary aggregation covering Rui’an city, Cangnan county,Pingyang county, and Wencheng county, from January 1, 2014, to December 31, 2018, with a radiation radius of 44.67km (LLR=12 534.45, RR=1.98, P < 0.01). The proportion of enterovirus type 71 (EV-A71) in group A showed a downward trend (χ²_trend=171.245, P < 0.05), while the proportion of other enteroviruses, including coxsackievirus group A 16 (CV-A16), increased(χ²_trend=93.481, P < 0.05). Conclusion The incidence of HFMD in Wenzhou remains high, although both the incidence and severity rates have decreased. Other enteroviruses, including coxsackievirus group A 6 (CV-A6), have become the dominant pathogens, and there has been an increase in incidence among teachers and individuals over 6 years old. The main aggregation areas were identified as Rui’an city, Cangnan county, Pingyang county, and Wencheng county.