Purpose. To evaluate the clinical and in vivo confocal microscopy outcome of lamellar keratoplasty combined with amniotic membrane transplantation for the treatment of corneal perforations. Methods. In this retrospective, noncomparative, and interventional case series, 13 eyes of 13 patients with corneal perforation were included. All eyes were treated with lamellar keratoplasty combined with amniotic membrane transplantation for corneal reconstruction. Age, underlying etiology, location, size of corneal ulcer, size of corneal perforation, hospitalization days and follow-up time, and corneal confocal microscopy were investigated. Aqueous leakage, anterior chamber formation, epithelial healing time, and visual acuity (VA) were monitored after operation. Results. The cause of corneal perforation (n = 13) was classified as infectious (n = 1) and noninfectious (n = 12). Most of the locations of corneal perforation were paracentral, and 2 of them were center. The anterior chambers were formed without aqueous leakage and other complications at postoperative day. The mean time of regained a smooth corneal surface was 7.5 ± 2.9 (ranging from 4 to 14) days. The mean hospitalization day was 13.1 ± 4.5 (ranging from 7 to 22) days. The mean follow-up time is 22.5 ± 14.5 (ranging from 4 to 43) months. The AM appeared as a high-reflective reflection in the corneal stroma after surgery about half a year and is almost transparent at about one year. Corneal stroma-derived cells were populated in the AM at about 1 month, increased at 2 months, and almost not obviously at 20 months postoperatively. The size and density of endothelial cells were stable after 1 year near the perforation site. The VA improved to varying degrees in 9 eyes, remained unchanged in 2 eyes, and decreased in 2 eyes. One eye recurrence and no side effects occurred during the follow-up time. Conclusion. Lamellar keratoplasty combined with amniotic membrane transplantation may be an alternative, safe, and effective surgical therapy in the treatment of corneal perforations in the absence of a fresh donor cornea. We recommend this surgery to treat with the size of corneal perforation of <4 mm in diameter no matter peripheral or central corneal perforation, especially who had immune-related diseases.