Objective The first‐line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters. Methods Based on the obesity patient follow‐up registry the APV (Adipositas‐Patienten‐Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 IQR: 9.7–13.2 years; BMI z score BMIz: 2.06 IQR: 1.79–2.34; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k‐means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership. Results A total of 36.3% of children and adolescents experienced “no BMIz loss.” The largest subcluster (44.8%) achieved “moderate BMIz loss,” with an average delta‐BMIz of −0.23 (IQR: −0.33 to −0.14) at study end. A total of 18.9% had a “pronounced BMIz loss” up to −0.61 (IQR: −0.76 to −0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05). Conclusions These results support the importance of patient‐tailored intervention and earlier treatment escalation in high‐risk individuals who have little chance of success.