Objective: Cognitive–behavioral models of chronic fatigue syndrome (CFS) propose that patients respond to symptoms with 2 predominant activity patterns—activity limitation and all-or-nothing behaviors—both of which may contribute to illness persistence. The current study investigated whether activity patterns occurred at the same time as, or followed on from, patient symptom experience and affect. Method: Twenty-three adults with CFS were recruited from U.K. CFS services. Experience sampling methodology (ESM) was used to assess fluctuations in patient symptom experience, affect, and activity management patterns over 10 assessments per day for a total of 6 days. Assessments were conducted within patients’ daily life and were delivered through an app on touchscreen Android mobile phones. Multilevel model analyses were conducted to examine the role of self-reported patient fatigue, pain, and affect as predictors of change in activity patterns at the same and subsequent assessment. Results: Current experience of fatigue-related symptoms and pain predicted higher patient activity limitation at the current and subsequent assessments whereas subjective wellness predicted higher all-or-nothing behavior at both times. Current pain predicted less all-or-nothing behavior at the subsequent assessment. In contrast to hypotheses, current positive affect was predictive of current activity limitation whereas current negative affect was predictive of current all-or-nothing behavior. Both activity patterns varied at the momentary level. Conclusions: Patient symptom experiences appear to be driving patient activity management patterns in line with the cognitive–behavioral model of CFS. ESM offers a useful method for examining multiple interacting variables within the context of patients’ daily life.