Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) among animals and humans are a public health threat. This study analyzed the occurrence of ESBL-E in a high-risk environment in a companion animal clinic and two animal patients’ households. In an intensive care unit (ICU), rectal swabs from 74 dogs and cats, 74 hand swabs from staff and 298 swabs from surfaces were analyzed for ESBL-E. Seventeen hospitalized patients (23%) and ten (3%) surfaces in the ICU tested ESBL-E positive. Transmission chains for Klebsiella pneumoniae ST307 blaCTX-M-15 and Escherichia coli ST38 blaCTX-M-14, ST88 blaCTX-M-14 and ST224 blaCTX-M-1 were observed over extended periods of time (14 to 30 days) with similar strains isolated from patients and the clinical environment. After discharge, two colonized dogs (dogs 7 and 12) and their household contacts were resampled. Dog 7 tested repeatedly positive for 77 days, dog 12 tested negative; six (24%) surfaces in the household of the persistently colonized dog tested ESBL-E positive. The owner of dog 7 and one of the owners of dog 12 were colonized. Based on whole genome sequencing, isolates from the owners, their dogs and other ICU patients belonged to the same clusters, highlighting the public health importance of ESBL-E in companion animal clinics.