Objectives: To investigate hospital admissions in England and Wales due to infections and diseases of the skin and subcutaneous tissue. Methods: Data from the Patient Episode Database for Wales (PEDW) and the Hospital Episode Statistics (HES) database in England for the years between April 1999 and April 2020 were used in this study. Using all the relevant diagnosis codes (L00–L99), hospital admissions related to various skin infections and diseases of the subcutaneous tissue were identified. Results: Hospital admissions for all causes increased overall by 78.8%, from 276,464 in 1999 to 494,433 in 2020, representing an increase in hospital admission rate of 56.1% (from 530.23 (95% CI 528.26–532.20) in 1999 to 827.92 (95% CI 825.62–830.22) per 100,000 people in 2020, p ≤ 0.05). The most prevalent diagnoses were disorders of the skin’s appendages, infections of the skin and subcutaneous tissue, and other disorders of the skin and subcutaneous tissue. Nearly half of all hospital admissions were for males and for patients between the ages of 15 and 59. In 2020, the hospital admission rate for males increased by 60.2%, from 540.16 (95% CI 537.32–543.01) per 100,000 people in 1999 to 865.10 (95% CI 861.76–868.44) in 2020. From 520.75 (95% CI 518.02–523.48) in 1999 to 791.03 (95% CI 787.86–794.19) in 2020, the hospital admission rate for females grew by 51.9%. Conclusion: Hospital admission due to infections and disorders of the skin and subcutaneous tissue increased during the past two decades in England and Wales. Further studies are needed to explore the risk factors associated with infections and disorders of the skin and subcutaneous tissue complications, and its associated admissions.