Objective To compare the efficacy and safety of 1064-nm Nd:YAG picosecond fractional laser and ultra-pulsed CO2 fractional laser in the treatment of facial atrophic acne scars. Methods A total of 62 patients with facial atrophic acne scars who were treated in the laser department of our hospital from June 2021 to June 2023 were selected as the research objects. According to different treatment methods, they were divided into picosecond fractional laser group and CO2 fractional laser group, with 31 patients in each group. The picosecond fractional laser group was treated with 1064-nm Nd:YAG picosecond lattice laser, and the CO2 fractional laser group was treated with ultra-pulsed CO2 fractional laser. The ECCA score, self-efficacy score, satisfaction score and postoperative adverse reactions were compared between the two groups. Results After treatment, the ECCA score of the two groups was lower than that before treatment (P <0.05), and the ECCA score of the picosecond fractional laser group was higher than that of the CO2 fractional laser group (P <0.05). The self-assessment efficacy score of the CO2 fractional laser group was higher than that of the picosecond fractional laser group (P <0.05). The incidence of adverse reactions in the picosecond fractional laser group was lower than that in the CO2 fractional laser group (P <0.05). There was no significant difference in satisfaction between the two groups (P >0.05). Conclusion Both 1064-nm Nd:YAG picosecond fractional laser and ultra-pulsed CO2 fractional laser can effectively improve facial atrophic acne scars. Ultra-pulsed CO2 fractional laser has better curative effect, while picosecond fractional laser has fewer adverse reactions.