Abstract Background The knowledge, skills, and confidence to manage one’s own health is termed patient activation and can be assessed using the Patient Activation Measure (PAM). This measure is increasingly recommended for use in chronic kidney disease (CKD), but there is a need to better understand patient activation within this population. This work aimed to explore the association of PAM with patient-reported outcomes, namely symptom burden and health-related quality of life (HRQoL), to understand the relationship between patient activation and outcomes which are of importance to people with CKD. Methods Non-dialysis, dialysis, and kidney transplant patients from 14 renal units across England completed a survey comprising questionnaires assessing patient activation, symptom burden, and HRQoL. Latent class analysis (LCA) was used to determine HRQoL and symptom burden subgroups in the data. Multinomial logistic regression analyses were performed to investigate the associations between patient activation and symptom burden and HRQoL classes separately, adjusting for age, gender, ethnicity, deprivation and treatment modality. Results Three thousand thirteen participants (mean age 61.5 years, 61.8% males, and 47% haemodialysis) were included in the analysis. Patient activation was strongly associated with both the HRQoL and symptom burden classes identified, with highly activated patients more likely to report higher HRQoL (P = < 0.0001; OR 29.2, 95% CI 19.5–43.9) and fewer symptoms (P = < 0.0001; OR 25.9, 95% CI 16.8–40.2). Conclusion Lower activation levels are associated with a higher symptom burden and reduced HRQoL across the trajectory of CKD stages and treatment modalities. Therefore, targeted and holistic self-management support focussing on improving activation may have the potential to improve aspects of health experience which are valued by individuals living with kidney disease.