Background/objectives: Multi-ligament knee injuries (MLKIs) present complex surgical challenges, and there remains no consensus on whether single-stage or staged reconstruction yields superior outcomes. This study aimed to assess differences in complications, functional outcomes, and return-to-sport rates between single-stage and staged surgical approaches. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines. Four databases (PubMed, Scopus, Embase, and the Cochrane Library) were searched for studies published between 2000 and 2025. Eligible studies reported surgical management of MLKIs and specified either single-stage or multi-stage reconstruction. Data on complications, functional scores (Lysholm), return to sport, rehabilitation protocols, and graft type were extracted and analyzed using descriptive statistics and study-level regression models. Results: A total of 43 studies encompassing 2086 patients were included (1900 single-stage; 186 multi-stage). Staged reconstruction was associated with a significantly lower rate of arthrofibrosis (1.95% vs. 7.29%; OR 3.96, p = 0.007), higher Lysholm scores (+4.7 points, p < 0.001), and higher return-to-sport rates (48% vs. 65%, p = 0.001) compared to single-stage. Use of synthetic grafts increased the risk of arthrofibrosis (OR 4.09, p = 0.031). Early mobilization and weightbearing were not associated with increased arthrofibrosis risk. Conclusions: Staged reconstruction may yield better functional outcomes and lower complication rates—particularly arthrofibrosis, compared to single-stage approaches. These findings support an individualized surgical strategy, guided by injury complexity, graft selection, rehabilitation goals, and patient-specific functional demands.