Shigella sonnei has become the dominant serotype causing shigellosis in Asian countries in recent years. In this study, we characterize the increasing trend of antibiotic resistance profiles and genotypes of S. sonnei isolates in the Beijing area. From January 2002 to December 2007, a total of 1108 Shigella isolates including 362 S. sonnei were recovered from diarrhea patients at the 302nd Hospital in Beijing. While the frequency of S. flexneri gradually decreased, S. sonnei gradually increased and became the dominant species. A total of 362 S. sonnei isolates were further analyzed for their antimicrobial profiles and 272 revived isolates were selected for genotyping analysis, respectively. High-level antimicrobial resistances were observed in sulfamethoxazole/trimethoprim (94.5%), ampicillin (40.3%), piperacillin (36.5%), and ceftriaxone (12.8%) with significant single- and multiple-drug resistance increase trends from 2002 to 2007 (P = 0.0000). Pulsed-field gel electrophoresis analysis indicated that 263 (96.7%) S. sonnei belonged to 1 clonal genotype A, which were further divided into A1-A6 subtypes. While subtype A2 was dominant in the early stage of study years, subtype A4 started to emerge and increased significantly in later years. Antimicrobial resistance rates are statistically different among the 6 subtypes (P = 0.0000), and A4 possessed the highest resistance rates to ampicillin (83.7%) and piperacillin (81.4%). Subtype A3 was highly clustered in inpatients compared to other subtypes (P = 0.0145). This study indicates that a clonal S. sonnei strain has become dominant in the Beijing area, and subtype A4 is responsible for increased antibiotic resistance.