This study aims to explore the clinical efficacy and feasibility of preoperative 1-week chemotherapy for patients with spinal tuberculosis (STB) undergoing complete lesion removal. Clinical data of 76 patients with STB who underwent complete focal debridement in our hospital were collected from June 2020 to September 2023. The patients were divided into 38 cases of preoperative 1-week chemotherapy group (Group A) according to the length of preoperative chemotherapy, and 38 cases of preoperative 2 to 4-week chemotherapy group (Group B). Perioperative related, imaging, and laboratory examination indices as well as postoperative neurological function recovery, postoperative pain recovery, related complications, and clinical efficacy were analyzed to compare the clinical efficacy of the 2 groups. All patients successfully completed the treatment of stage I complete lesion removal combined with bone grafting fusion and internal fixation. The difference in erythrocyte setting rate and C-reactive protein at the same postoperative observation time between the 2 groups was not statistically significant (P > .05). The visual analogue scale scores of patients in the 2 groups decreased significantly with prolonged time, and the difference was statistically significant (P < .05). All patients achieved satisfactory clinical efficacy (P < .05). All patients achieved good clinical outcomes, the difference between the groups was not statistically significant (P > .05). The difference in incision healing rate at 3 months postoperatively and bone graft fusion rate at 6 months postoperatively was not statistically significant between the 2 groups (P > .05). The dissemination and recurrence of Mycobacterium tuberculosis were not statistically significantly different between the 2 groups after surgery (P > .05). In summary, with complete lesion clearance, 1 week of preoperative chemotherapy is feasible in patients with STB with varying degrees of neurological dysfunction.