Genetic association studies and meta-analyses of alcohol dependence (AD) have reported AD-associated single nucleotide polymorphisms (SNPs). These SNPs collectively account for a small portion of estimated heritability in AD. Recent genome-wide copy number variation (CNV) studies have identified CNVs associated with AD and substance dependence, suggesting that a portion of the missing heritability is explained by CNV. We applied PennCNV and QuantiSNP CNV calling algorithms to identify consensus CNVs in five AD cohorts of European and African origins. After rigorous quality control, genome-wide meta-analyses of CNVs were carried out in 3243 well-diagnosed AD cases and 2802 controls. We identified nine CNV regions, including a deletion in chromosome 5q21.3 with a suggestive association with AD (OR = 2.15 (1.41-3.29) and P = 3.8 × 10− 4) and eight nominally significant CNV regions. All regions were replicated with consistent effect sizes across studies and populations. Pathway and gene-drug interaction enrichment analyses based on the resulting genes indicated the mitogen-activated protein kinase signaling pathway and the recombinant insulin and hyaluronidase drugs, which were relevant to AD biology or treatment. To our knowledge, this is the first genome-wide meta-analysis of CNVs with addiction. Further investigation of the AD-associated CNV regions will provide better understanding of the AD genetic mechanism.