Increasing numbers of pertussis cases have been reported in recent years. The reported cases from Shenzhen Children's Hospital were close to one tenth of all cases in China. The epidemiology of antigenic genotype and antibiotic resistance of circulating strains in children have been unknown in Shenzhen, southern China. The aim of this study was to describe the clinical features and explore the genotypes and antimicrobial susceptibility of circulating Bordetella pertussis among children in Shenzhen. Data of hospitalized children with pertussis in Shenzhen Children's Hospital from August 2015 to April 2017 were collected. The genetic variability of isolates was investigated and Etest was performed for phenotypic susceptibility to erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole. 469 children with pertussis confirmed by real-time quantitative polymerase chain reaction were hospitalized and strains were isolated from 105 patients. White blood cell count ≥ 20 × 109/L and lymphocyte proportion ≥ 60% were observed in 39.29% of infants younger than 3 months. The two predominant profiles of virulence-associated allelic genes were ptxA1/ptxC1/ptxP1/prn1 (48.6%) and ptxA1/ptxC2/ptxP3/prn2 (44.8%). Among the isolates, 48.6% (51/105) were found resistant to macrolides. These findings indicate that leukocytosis is not a sensitive indicator of pertussis. Isolates with the gene profile ptxP3/prn2 were highly circulating in Shenzhen and less resistant to macrolides, different from patterns observed in other parts of China.