Changchun, the capital of northeastern Jilin Province and an important industrial base, ordered residents to stay at home, allowing one person out every two days to buy "daily necessities", AFP reported.
The city also halted all public transport, ordered schools and businesses shut and said it would institute mass testing.
China's daily coronavirus case count soared past the 1,000 mark this week for the first time since the pandemic's early days in 2020.
That is up from fewer than 100 cases just three weeks ago as the highly transmissible Omicron variant challenges China's zero-COVID approach to tackling the pandemic.
COVID-19 was first detected in China in late 2019 but the government has kept its case count extremely low by international standards with a combination of snap lockdowns, mass testing and largely closed borders.
There were 1,369 cases across more than a dozen provinces, according to Friday's daily official count.
Jilin, which has reported hundreds of cases in recent days, is one of more than a dozen provinces facing upticks along with major cities like Beijing and Shanghai.
Shanghai on Friday ordered its schools to close and shift to online instruction for the foreseeable future after dozens of cases emerged in the eastern economic hub in recent days.
And as cases increased, the country's National Health Commission announced Friday that they would introduce the use of rapid antigen tests.
The government has invested much of its prestige in its ability to control COVID-19, and Friday's measures appeared to pour cold water on hopes China would scrap its disruptive zero-tolerance approach anytime soon.
Mainland China's most recent major lockdown came in December when the city of Xi'an kept its 13 million people home for two weeks due to an outbreak.
But in the face of rising pandemic fatigue, top Chinese officials have in recent weeks urged local officials throughout the country to avoid such drastic steps.