Objective: A new diagnosis of pediatric cancer may disrupt family functioning. The current study aimed to describe changes in family rules and routines during the first year of pediatric cancer treatment, and to explore associations with demographics, illness factors, and caregiver distress. Methods: This exploratory mixed‐methods, cross‐sectional study examined 44 primary caregivers of youth in treatment for a new cancer diagnosis in 2019 and 2020, before the onset of the COVID‐19 pandemic. Caregivers completed validated questionnaires assessing demographic and child illness characteristics, psychosocial distress, and cancer‐related stressors, and participated in a semi‐structured interview about family rules and routines. Results: Caregivers reported changes in bedtime, mealtime, and school routines, relaxed behavioral expectations and rules around screen time, and new rules and routines around treatment, medications, and infection control. Caregivers with elevated levels of psychosocial distress reported more changed routines than caregivers with low levels of psychosocial distress. Caregivers who endorsed more cancer‐related stressors reported more new rules and routines than those who reported fewer cancer‐related stressors. Demographic and illness factors were not significantly associated with the number of changed, new, or stable family rules and routines. Conclusions: Families may relax rules and routines during the first several months of diagnosis, and this may be related to side effects of treatment and limited caregiver capacity. The long‐term impact of changes in family rules and routines during cancer treatment warrants further study given that accommodating parenting strategies have been associated with adverse short‐ and long‐term child health and behavior outcomes.