<b>Background/Objectives:</b> Traditional treatment for chronic osteomyelitis is temporary implantation of antibiotic-impregnated cement beads, followed by bone grafting after the infection is controlled. In this way, a staged operation is needed, and undergoing repetitive general anesthesia is a burden. Moreover, damage to the soft tissue at the surgical site due to several incisions is a concern. This study was conducted to investigate the outcomes of one-stage antibiotic-mixed cement blocks, instead of beads, used as a primary salvage procedure to treat chronic osteomyelitis of the foot, ankle, and lower leg. <b>Methods:</b> Twenty patients with chronic osteomyelitis of the leg and foot were included. They underwent complete debridement of the infected bone, and antibiotic-mixed cement fillings were placed into the defected bone space. Full-weight-bearing activities were allowed immediately after surgery. <b>Results:</b> For 16 of the 18 patients, infection was controlled after one-time surgery. Repeat antibiotic cement-filling surgery was necessary for two patients. Two-staged surgery with continuous irrigation and cement filling was necessary for one large tibial lesion. Conversion into arthrodesis of the metatarsophalangeal joint was necessary for metatarsal head infection. <b>Conclusions</b>: One-stage surgery with complete debridement and antibiotic-mixed cement filling is a simple and effective procedure for treating intractable chronic osteomyelitis, which makes full-weight-bearing walking possible immediately after surgery.