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Objective: This study was designed to compare the effects of hamstring muscle injection of botulinum toxin type A (BoNT/A) combined with periarticular injection to those of simple periarticular injection alone, in terms of early pain reduction and functional recovery following total knee arthroplasty (TKA). Methods: This study included 40 patients who underwent elective unilateral TKA at our hospital from February 2021 to December 2021. The patients were randomly assigned to either the experimental group (BoNT/A injection into the hamstring muscle + periarticular injection, n = 20 cases) or the control group (0.9% normal saline injection into the hamstring muscle + periarticular injection, n = 20 cases). The preoperative and postoperative 3-day HSS scores were compared between the two groups. Postoperative visual analog scale (VAS) pain scores were observed and compared between the two groups. The Lovett grading method was used to evaluate the postoperative muscle strength of both groups. Additionally, postoperative knee joint pain scores, maximum active flexion angle, and any postoperative adverse reactions were observed and compared between the two groups. Results: The experimental group showed significantly lower VAS pain scores than the control group at 24 h, 48 h, and 72 h after the operation, with a statistically significant difference (P < 0.05). Furthermore, compared to the control group, the patients in the experimental group exhibited larger knee joint active flexion angles at 1 day, 3 days, and 5 days post-operation, also demonstrating a statistically significant difference (P < 0.05). These findings hold scientific significance (P < 0.05). Additionally, the combined administration of BoNT/A hamstring muscle injection with periarticular injection exhibited a low incidence of adverse reactions during the perioperative period and had no significant effect on quadriceps muscle strength. Conclusion: The combination of BoNT/A hamstring muscle injection with periarticular injection effectively alleviates early postoperative pain following TKA and promotes early functional recovery of the knee joint.