Objective To understand the antimicrobial resistance of Escherichia spp. from member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021. Methods According to the technical scheme of China Antimicrobial Resistance Surveillance System (CARSS), data about Escherichia spp. and the antimicrobial susceptibility testing results reported from member units of Hunan Province Antimicrobial Resistance Surveillance System were analyzed by WHONET 5.6 software. Results From 2012 to 2021, a total of 476 351 clinically isolated Escherichia spp. were collected, 475 520 of which were Escherichia coli, accounting for 99.8%; 92.6% were isolated from inpatients; 39.3% were isolated from urine specimens. Over the past 10 years, the proportion of Escherichia spp. in total detected pathogens remained relatively stable, ranging 20%-23%, the lowest rate was 18.7% in 2012, and the highest rate was 22.9% in 2015. In the past 10 years, the resistance rates of Escherichia spp. to ampicillin, ceftriaxone, cefotaxime and ampicillin/sulbactam were >80%, >47%, >45%, and >39%, respectively; resistance rates to piperacillin/tazobactam, cefoperazone/sulbactam, and nitrofurantoin were all <8%, to tigecycline, amikacin, imipenem, and meropenem (except in 2012) were all <5%. Resistance of Escherichia spp. to 22 commonly clinically used antimicrobial agents fluctuated, but overall trend decreased year by year. The resistance rates of Escherichia spp. from patients in the intensive care unit (ICU), non-ICU patients, outpatients, and emergency patients to 22 clinically commonly used antimicrobial agents were compared among different departments, and the differences were statistically significant (all P<0.05). The resistance rates of Escherichia spp. isolated from ICU and non-ICU patients were compared, and except for tigecycline, the resistance rates to the other 21 antimicrobial agents were statistically different (all P<0.05). The resistance rates of Escherichia spp. isolated from patients to commonly clinically used antimicrobial agents were statistically different among patients of different age groups (all P<0.05). Conclusion Escherichia spp. isolated from patients in different years, departments, specimens, and ages have different resistance to commonly used antimicrobial agents. It is necessary to continue to strengthen the surveillance on bacterial resistance, so as to guide the rational choice of antimicrobial agents.