Objective: To analyze the therapeutic effect of ultra-pulsed CO2 fractional laser combined with microneedle therapy in the treatment of acne atrophic scars. Methods: 100 patients with acne atrophic scars admitted to our hospital from January 2024 to December 2025 were selected and randomly divided into the study group (ultra-pulsed CO2 fractional laser combined with microneedle therapy) and the control group (ultra-pulsed CO2 fractional laser), with 50 cases in each group. The therapeutic effects of the two groups were compared. Results: The therapeutic effect of the study group was better than that of the control group (P < 0.05); the ECCA score and transepidermal water loss of the study group were lower than those of the control group, and the keratin layer water content was higher than that of the control group (P < 0.05); there was no difference in the adverse reaction rate between the two groups (P > 0.05), and the total recurrence rate of the study group was lower than that of the control group, and the satisfaction rate was higher than that of the control group (P < 0.05). Conclusion: Ultra-pulsed CO2 fractional laser combined with microneedle therapy has a good therapeutic effect on acne atrophic scars.