Early identification of severe acute pancreatitis (SAP) is critical for clinical decision-making. The apolipoprotein B-to-apolipoprotein A1 ratio (ApoB/A1 ratio) reflects the balance between pro-inflammation and anti-inflammation in vivo. This study investigated the association between serum ApoB/A1 ratio at admission and acute pancreatitis (AP) severity. A total of 375 patients with first attack of AP were retrospectively recruited from January 2014 to December 2017. The severity of AP was assessed at admission based on the 2012 revised Atlanta Classification. Serum lipids levels were tested on the first 24 h of hospitalization, of which the correlations with clinical features or scoring systems were also measured. The ApoB/A1 ratio markedly increased across disease severity of AP. The ApoB/A1 ratio, expressed as both quartile and continuous variables, was significantly associated with a high risk of SAP, even after adjustment for other conventional SAP risk factors. The ApoB/A1 ratio positively correlated with the revised 2012 Atlanta Classification, Ranson score, Bedside Index for Severity in AP score, Modified Computed Tomography Severity Index score, and Acute Physiology and Chronic Health Evaluation II score for AP severity. The optimal cut-off value of ApoB/A1 ratio for detecting SAP was 0.88, with a sensitivity of 83.08% and a specificity of 69.03%. Serum ApoB/A1 ratio at admission is closely correlated with disease severity in patients with AP and can serve as a reliable indicator for SAP in clinical setting.