The present study aimed to develop a commercial active packaging system of ground beef, by exploiting the antimicrobial and antioxidant properties of a traditional Greek alcoholic distillate called “tsipouro”. Commercial packages (500 g) were used and 40 mL of “tsipouro” was added in absorbent pads placed underneath the ground beef, while 10 mL was also mounted under the packaging film, facing the headspace. Samples were packaged in 80% O2: 20% CO2 and stored at 0, 4, 8, and 12 °C. Total Viable Counts, pseudomonads, Brochothrix thermosphacta, lactic acid bacteria, yeasts-moulds, pH, colour (L*, a*, b*), odour (buttery and acidic), and ethanol migration to ground beef (SPME/GC-FID) were determined. Moreover, mathematical models (square root and Arrhenius) describing the effect of temperature on determinant indicators of spoilage and quality deterioration like growth of dominant microorganisms and red colour reduction were developed and validated under non-isothermal conditions. B. thermosphacta dominated the microbial association of ground beef, while LAB were second in dominance, revealing a high growth potential at all assays. a* value (redness) was gradually decreased in controls, while samples treated with “tsipouro” showed more stable red colour during storage. Although ethanol was organoleptically detectable, especially at low storage temperatures (0–4 °C), it was rather perceived as a pleasant cool odour. Prediction by both models for microbial growth as well as those of Arrhenius model for reduction of a* value showed good agreement with the observations under non-isothermal storage. Overall, our study showed that the developed antimicrobial active packaging of ground beef based on “tsipouro”, combined with high oxygen MAP lead to an almost 2-fold shelf-life extension compared with controls during storage at chill and abuse temperatures.