Background Nickel-titanium (NiTi) archwires are routinely used for initial leveling and alignment of teeth in orthodontic treatment. This study aimed to clinically compare the level of pain and tooth alignment in orthodontic treatment with A-NiTi versus Cu-NiTi archwires. Methods In this parallel randomized clinical trial, 88 orthodontic patients (12–25 years) with an irregularity index > 2 mm in the anterior site of the lower dental arch who required non-extraction orthodontic treatment of the lower arch were randomized into two age- and sex-matched groups (n = 44) for treatment with A-NiTi and Cu-NiTi initial archwires. Each archwire was used for 6 weeks. After 6 weeks, the irregularity index was measured, and the level of pain was scored using the Modified McGill pain questionnaire (MPQ) and visual analog scale (VAS) according to the time of onset and duration of pain, and analgesic intake. Data were analyzed by paired t test, independent samples t test, and Chi-square test (P < 0.05). Results The irregularity index significantly decreased in both groups after 6 weeks of treatment (P < 0.001). However, the difference in this respect was not significant between the two groups (P > 0.05). Pain perception (P = 0.487), duration of pain (P = 0.546), and analgesic intake (P = 0.102) were not significantly different between the two groups either. Conclusion Both A-NiTi and Cu-NiTi archwires are equally effective for tooth alignment in the anterior site of the lower dental arch and have no significant difference with regard to the level of pain experienced by patients. Trial registration number: IRCT20190705044102N1 and Name of the registry: Iranian registry of clinical trials (https://irct.ir/) Date of registration: September, 26, 2019