The objective of this study was to identify potential genetic variants and positional candidate genes associated with growth and feed efficiency traits in American mink. Genome-wide association studies (GWAS) were performed using deregressed estimated breeding values of 1037–1872 individuals (as pseudophenotypes), genotyped with the Affymetrix Mink 70K single nucleotide polymorphism (SNP) array. A total of 42 SNPs located on 11 different chromosomes were significantly (false discovery rate < 0.01) associated with six growth and feed efficiency traits. Furthermore, 153 genes were identified within 1-Mb windows flanking these significant SNPs. Several positional candidate genes such as TUBB, CDKN1A, SRSF3, GPRC6A, RFX6, and KPNA5 were previously associated with feed efficiency and growth traits in other livestock species. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that these genes were involved in lipid metabolism, hormone signaling and regulation, and muscle development. To our knowledge, this is the first GWAS to identify genetic variants and biological mechanisms associated with growth and feed efficiency traits in American mink. These findings provide a biological foundation for improving these traits using genomic selection programs to select more efficient mink.