Background: Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide, with epidermal growth factor receptor (EGFR) inhibitors improving outcomes in patients with metastatic CRC (mCRC) harboring KRAS wild-type tumors. Inflammation has emerged as a potential determinant of treatment efficacy, and the neutrophil-to-lymphocyte ratio (NLR) represents an accessible biomarker reflecting the balance between protumoral neutrophils and antitumor lymphocytes. Methods: We conducted a retrospective study of 44 patients with left-sided, KRAS wild-type mCRC treated at the Institute of Oncology “Prof. Dr. Ion Chiricuta” between 2015 and 2024 with first-line FOLFOX/FOLFIRI plus panitumumab. Baseline NLR (bNLR) and NLR after four treatment cycles were assessed, with progression-free survival (PFS) as the primary endpoint. Results: Receiver operating characteristic analysis identified an optimal bNLR cutoff of 3.06 (AUC = 0.78, p = 0.004). Patients with low bNLR (≤3.06) had significantly longer PFS than those with high bNLR (>3.06) (14 vs. 7 months, HR = 2.7, p = 0.002). Notably, patients with a positive ΔNLR (increase during therapy) also demonstrated superior PFS compared to those with a negative ΔNLR (18 vs. 11 months, HR = 0.47, p = 0.022). In multivariate analysis, only bNLR remained independently associated with PFS. Conclusions: These results suggest that both baseline and dynamic NLR may serve as low-cost prognostic biomarkers in mCRC patients treated with anti-EGFR therapy.