Selection of archwire sequence plays a critical role in determining the efficiency, biological response, and patient experience during fixed orthodontic treatment. This randomized controlled trial evaluated the effectiveness of two commonly used archwire sequences in achieving dental alignment and reducing treatment-related discomfort. A total of 120 patients requiring comprehensive fixed appliance therapy were randomly allocated into two groups: a conventional nickel–titanium to stainless steel sequence and a modified superelastic nickel–titanium sequence. Primary outcomes included rate of dental alignment measured using Little’s Irregularity Index and treatment efficiency over the first six months. Secondary outcomes included pain intensity and chairside adjustment time. The modified superelastic sequence demonstrated significantly faster alignment at 12 and 24 weeks (p < 0.001) and lower mean pain scores during initial stages (p = 0.002). No significant difference was observed in overall bracket failure rates. These findings indicate that archwire sequencing influences early treatment efficiency and patient comfort. This study provides novel randomized evidence supporting optimized archwire selection to enhance biologic response and clinical efficiency in orthodontic therapy.