Wuhua yellow chicken (WHYC) is an important traditional yellow-feathered chicken from China, which is characterized by its white tail feathers, white flight feathers, and strong disease resistance. However, the genomic basis of these unique traits associated with WHYC is poorly understood. In this study, whole-genome resequencing was performed with an average coverage of 20.77-fold to investigate heritable variation and identify selection signals in WHYC. Reads were mapped onto the chicken reference genome (Galgal5) with a coverage of 85.95%. After quality control, 11,953,471 single nucleotide polymorphisms and 1,069,574 insertion/deletions were obtained. In addition, 41,408 structural variants and 33,278 copy number variants were found. Comparative genomic analysis of WHYC and other yellow-feathered chicken breeds showed that selected regions were enriched in genes involved in transport and catabolism, immune system, infectious diseases, signal transduction, and signaling molecules and interactions. Several genes associated with disease resistance were also identified, including
IFNA
,
IFNB
,
CD86
,
IL18
,
IL11RA
,
VEGFC
, and
ATG10
. Furthermore, our results suggest that
PMEL
and
TYRP1
may contribute to the white feather coloring in WHYC. These findings can improve our understanding of the genetic characteristics of WHYC and may contribute to future breed improvement.