The objective of this study was to investigate the distribution of extended spectrum β-lactamase (ESBL)-producing Escherichia coli isolates in swine and poultry farms in China. Rectal or cloaca swabs of swine and chicken were collected from four province-level regions of China, and E. coli isolates were recovered and tested for antimicrobial susceptibility. The isolates producing ESBLs were further characterized by pulsed-field gel electrophoresis (PFGE) and sequence analysis of genes encoding β -lactamases and class I integrons. In total, 156 and 224 E. coli isolates were recovered from rectal swabs of four swine farms and cloaca swabs of six chicken farms, respectively. Prevalence of resistant isolates was higher in chicken than in swine. Fifty-six isolates producing ESBLs were identified from chicken samples, but no ESBL-producing isolates were identified from swine samples. Of 56 ESBL-producing isolates, 54 isolates contained cefotaxime (CTX)-M type β-lactamases, including bla(CTX-M-14) (n = 24), bla(CTX-M-65) (n = 13), bla(CTX-M-55) (n = 10), bla(CTX-M-24) (n = 3), bla(CTX-M-3) (n = 2), bla(CTX-M-15) (n = 1), and bla(CTX-M-64) (n = 1). Among 54 E. coli isolates containing bla(CTX-M), 11 PFGE clusters and 42 PFGE patterns were identified. More importantly, more than three-fourth of the ESBL-producing isolates in chicken were also resistant to ciprofloxacin. Our data demonstrated that chicken had become an important reservoir of bla(CTX-M) in China. Detailed molecular comparison of plasmids and genomes of isolates from various sources will help to better define the transmission dynamics of bla(CTX-M) between humans and food-producing animals.