"If nothing is done, the coronavirus will spread rapidly," Governor Naomichi Suzuki said. "This is a crucial moment. We must take unprecedented measures."
The declaration of emergency came after a number of people who attended a trade fair in Kitami City in mid-February were found to have been infected.
Officials say six people from the event have been confirmed to be infected so far, including a man in his 70s who is reportedly in serious condition. The officials fear the infections may be on a far larger scale, as about 700 people over three days took part in the fair.
The declaration has forced schools, companies, and residents throughout the prefecture to make adjustments.
All elementary and junior high schools were closed starting on Friday, and students will now be off for five weeks, until the end of the normal spring break. Meanwhile, many companies have implemented telework, or work from home, policies.
The declaration is taking a visible toll on the prefecture's businesses. Department stores in the major cities of Sapporo and Hakodate were closed over the weekend.
NHK spoke to shop owners on Saturday in Sapporo's Susukino District, which is a popular neighborhood for nightlife. The crowds were noticeably smaller.
"This is supposed to be the busiest time of year," said the owner of a barbecue restaurant. "The virus has been a huge blow to business."
Norio Ohmagari, from the National Center for Global Health and Medicine, is an infectious disease expert with experience advising the Japanese government.
He says the declaration was a smart move, given the increasing number of cases in the prefecture and the possibility of a rapid rise in infections from the Kitami cluster.
Japan's health ministry has sent officials to Hokkaido and Prime Minister Shinzo Abe has pledged large deliveries of face masks.
Doctors at the Hokkaido Medical Association announced on Sunday they will increase the number of beds at hospitals throughout the prefecture. Association head Kiyoshi Nagase described the situation as "unprecedented."
While the local and national governments make efforts to contain the outbreak, all the residents of Hokkaido can do is sit inside and wait for the situation to improve.