Background: Managing chronic conditions can overwhelm patients and reduce their confidence in self-management. Patient activation (PA) is a concept that reflects patients’ knowledge, skills, and confidence in managing their health and self-care. In Jordan, PA has not been explicitly studied, particularly among patients with chronic conditions. Therefore, this study explores PA and its determinants in individuals with chronic conditions in Jordan. Methods: A cross-sectional study was conducted using a convenience sample of outpatients recruited from a tertiary hospital in Jordan. Participants completed a questionnaire including sociodemographic and clinical data, the Single Item Literacy Screener, and the 13-item Patient Activation Measure (PAM). Bivariate and regression analyses were conducted to explore the factors associated with PAM scores. Results: Among a total of 666 participants, the mean PAM score was 57.1 ± 9.17, indicating a moderate activation level overall. Regression analysis revealed that being female (p = 0.14), adequate health literacy (p = 0.002), and post-secondary education (p = 0.004) were significantly associated with higher PAM scores, and older age (p = 0.004) and polypharmacy (p = 0.010) with lower scores. An additional regression model showed that the negative association between polypharmacy and PA scores did not differ by health literacy level, with no significant interaction between polypharmacy and health literacy (p = 0.555). Conclusions: This study showed that individuals with chronic illnesses in Jordan had moderate to high patient activation levels. Several sociodemographic and clinical factors were significantly associated with patient activation. Polypharmacy was independently associated with lower patient activation scores, regardless of health literacy levels. However, given the study’s exploratory nature, the results should be interpreted as preliminary evidence warranting further research.