Background: The optimal timing of surgical intervention for multiligament knee injuries remains controversial. Purpose: To review the clinical and functional outcomes after acute and delayed surgical intervention for multiligament knee injuries. Study Design: Systematic review; Level of evidence, 4. Methods: We performed a search of the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to September 2020. Eligible studies reported on knee dislocations, multiligament knee injuries, or bicruciate ligament injuries in adult patients (age, ≥18 years). In addition to comparing outcomes between acute and delayed surgical intervention groups, we conducted 3 subgroup analyses for outcomes within isolated knee injuries, knee injuries with concomitant polytrauma/fractures, and high-level (level 2) studies. Results: Included in the analysis were 31 studies, designated as evidence level 2 (n = 3), level 3 (n = 8), and level 4 (n = 20). These studies reported on 2594 multiligament knee injuries sustained by 2585 patients (mean age, 25.1-65.3 years; mean follow-up, 12-157.2 months). At the latest follow-up timepoint, the mean Lysholm (n = 375), International Knee Documentation Committee (IKDC) (n = 286), and Tegner (n = 129) scores for the acute surgical intervention group were 73.60, 67.61, and 5.06, respectively. For the delayed surgical intervention group, the mean Lysholm (n = 196), IKDC (n = 172), and Tegner (n = 74) scores were 85.23, 72.32, and 4.85, respectively. The mean Lysholm (n = 323), IKDC (n = 236), and Tegner (n = 143) scores for our isolated subgroup were 83.7, 74.8, and 5.0, respectively. By comparison, the mean Lysholm (n = 270), IKDC (n = 236), and Tegner (n = 206) scores for the polytrauma/fractures subgroup were 83.3, 64.5, and 5.0, respectively. Conclusion: The results of our systematic review did not elucidate whether acute or delayed surgical intervention produced superior clinical and functional outcomes. Although previous evidence has supported acute surgical intervention, future prospective randomized controlled trials and matched cohort studies must be completed to confirm these findings.