Background: First-line treatment options for patients with BRAF-mutated metastatic melanoma include dacarbazine (DTIC), dabrafenib (DAB), dabrafenib + trametinib (DAB+TRA), vemurafenib (VEM), and vemurafenib + cobimetinib (VEM+COB). The optimal treatment option is uncertain given the lack of direct head to head trial evidence. We aimed to indirectly estimate the comparative PFS and OS benefits of these treatment options. Methods: Following a search of PubMed, EMBASE, and Cochrane Library, a Bayesian network meta-analysis using a fixed effect model was performed to estimate hazard ratios (HRs) and 95% credible intervals (CrI) for PFS and OS for pairwise combinations of DTIC, DAB, DAB+TRA, VEM, and VEM+COB. Due to differences in length of follow up, HRs for PFS at month (m) 7 were calculated and utilized in sensitivity analyses. Results: Five randomized controlled trials (RCTs) involving 2,547 patients were included. For PFS, VEM+COB prevailed statistically (HR, 95%CrI) over DTIC (0.20, 0.14–0.28), DAB (0.61, 0.42–0.90), VEM (0.51, 0.39–0.68), but not DAB+TRA (0.89, 0.63–1.25); and DAB+TRA prevailed over DTIC (0.23, 0.18–0.29), DAB (0.69, 0.56–0.85), and VEM (0.57, 0.48–0.69). For OS, VEM+COB prevailed statistically over DTIC (0.49, 0.31–0.80) but not DAB (0.67, 0.40–1.14), VEM (0.65, 0.42–1.01), and DAB+TRA (0.92, 0.56–1.51); DAB+TRA prevailed over DTIC (0.54, 0.41–0.71), DAB (0.73, 0.58–0.92), and VEM (0.71, 0.56–0.89). In sensitivity analyses for calculated 7m PFS, VEM+COB prevailed statistically over DTIC (0.15, 0.28–0.73), DAB (0.45, 0.28–0.73), VEM (0.48, 0.34–0.69), but not DAB+TRA (0.77, 0.50–1.20); DAB+TRA prevailed over DTIC (0.19, 0.14–0.26), DAB (0.58, 0.44–0.77), and VEM (0.62, 0.48–0.80). Conclusions: This indirect treatment comparison demonstrates comparable PFS and OS benefits for VEM+COB and DAB+TRA. In addition, DAB+TRA but not VEM+COB may offer a modest OS benefit over VEM and DAB.