Dairy cream, a common ingredient in various dishes and food products, is susceptible to rapid microbial growth due to its high water activity (≈0.97) and pH (≈6.7). Thus, it requires proper processing conditions to ensure food safety and extend shelf life. High-pressure processing (HPP) has emerged as a nonthermal food pasteurization method, offering an alternative to conventional heat-based techniques to obtain tastier, fresh-like, and safe dairy products without undesirable heat-induced alterations. This study assessed the impact of HPP (450 and 600 MPa for 5 and 15 min at 7 °C) and thermal pasteurization (75 °C for 15 s) on the microbiological and physicochemical attributes of dairy cream immediately after processing and throughout refrigerated storage (4 °C). HPP-treated samples remained microbiologically acceptable even on the 51st day of storage, unlike thermally pasteurized samples. Moreover, HPP decreased inoculated Escherichia coli and Listeria innocua counts by more than 6 log units to undetectable levels (1.00 log CFU/mL). pH, color (maximum variation of ΔE* up to 8.43), and fatty acid profiles remained relatively stable under varying processing conditions and during storage. However, viscosity exhibited higher values for HPP-treated samples (0.028 ± 0.003 Pa·s) compared to thermally processed ones (0.016 ± 0.002 Pa·s) by the 28th day of storage. Furthermore, volatile compounds (VOCs) of all treated samples presented a tendency to increase throughout storage, particularly acids and aliphatic hydrocarbons. These findings show HPP’s potential to significantly extend the shelf life of highly perishable dairy cream by at least 15 days compared to thermal pasteurization.