Background: Umbilical cord patch (UCP) grafts have been successfully used for glaucoma shunt tube coverage and conjunctival surface reconstruction. In recent years, the technique has emerged as a novel alternative for the reconstruction of corneal perforation and descemetocele. This study aimed to evaluate the effectiveness of combined UCP grafting and human amniotic membrane (HAM) transplantation for the management of corneal perforation or descemetocele. Methods: This prospective, non-comparative, interventional case series included nine eyes of nine patients with corneal descemetoceles and 28 eyes of 28 patients with corneal perforations, all in a clinically quiescent state. UCP grafting and HAM transplantation were combined to treat all patients. We re-examined the patients daily throughout the first week, weekly for 1 month, and then monthly for the first 6 months using slit-lamp examination and anterior segment optical coherence tomography. Results: We included 37 eyes with descemetocele or corneal perforation in a clinically quiescent state. The mean (standard deviation) ages of patients with corneal descemetocele and corneal perforation were 56.3 (18.8) years and 54.3 (18.1) years, respectively. The male-to-female ratios in patients with corneal descemetocele and corneal perforation were 56% to 44% and 61% to 39%, respectively. Postoperative corneal thickness increased significantly in eyes with descemetocele compared to preoperative values (P < 0.001). Postoperative best-corrected distance visual acuity improved significantly compared to preoperative values in eyes with descemetocele or corneal perforation (both P < 0.001), with relief of accompanying ocular symptoms. We did not observe any recurrence or complications such as rejection, infection, suture-related problems, or severe inflammation and all had a formed anterior chamber up to the final follow-up visit. Conclusions: Combined UCP grafting and HAM transplantation could be a promising alternative treatment for corneal perforation or descemetocele in clinically quiescent eyes, providing satisfactory reconstruction and functional outcomes. Further studies with robust designs, larger sample sizes, and longer follow-up are needed to verify the efficacy and safety of this modified surgical technique in enhancing vision and restoring anterior segment anatomical integrity in compromised corneas.