Background: Sepsis is a leading cause of mortality in polytrauma patients, especially beyond the first week, and its management is vital for reducing multiorgan failure and improving survival rates. This is particularly critical in geriatric polytrauma patients due to factors such as age-related physiological alterations and weakened immune systems. This study aimed to investigate various clinical and laboratory parameters associated with sepsis in polytrauma patients aged < 65 years and ≥65 years, with the secondary objective of comparing sources of infection in these patient groups. Methods: A retrospective cohort study was conducted at the University Hospital Zurich from August 1996 to December 2012. Participants included trauma patients aged ≥16 years with an Injury Severity Score (ISS) ≥ 16 who were diagnosed with sepsis within 31 days of admission. Patients in the age groups < 65 and ≥65 years were compared in terms of sepsis development. The parameters examined included patient and clinical data as well as laboratory values. The statistical methods encompassed group comparisons with Welch’s t-test and logistic regression. Results: A total of 3059 polytrauma patients were included in the final study. The median age in the group < 65 years was 37 years, with a median ISS of 28. In the patient group ≥ 65 years, the median age was 75 years, with a median ISS of 27. Blunt trauma mechanism, ISS, leucocytosis at admission, and anaemia at admission were associated with sepsis in younger patients but not in geriatric patients, whereas sex, pH at admission, lactate at admission, and Quick values at admission were not significantly linked with sepsis in either age group. Pneumonia was the most common cause of sepsis in both age groups. Conclusions: Various parameters linked to sepsis in younger polytrauma patients do not necessarily correlate with sepsis in geriatric individuals with polytrauma. Hence, it becomes critical to recognize imminent danger, particularly in geriatric patients. In this context, the principle of “HIT HARD and HIT EARLY” is highly important as a proactive approach to effectively address sepsis in the geriatric trauma population, including the preclinical setting.