The closure, scheduled for June 16, will happen when the territory's public health emergency ends, along with the vaccine mandate for workers.
"The Centre for National Resilience will cease operations, but it will be ready to stand up if we as a territory or Australia need it," Ms Fyles told reporters on Thursday.
"It was that facility that when COVID first appeared in the world got Australians out of situations when they were stuck overseas.
"We saw thousands be able to come home through that facility, and it was something Territorians should be proud of."
Ms Fyles acknowledged the hundreds of AUSMAT and NT health staff who worked at the Howard Springs facility since it opened in late 2020.
At the centre's busiest, staff cared for up to 2000 people per fortnight, but it is currently empty.
Ms Fyles said the NT was working with the Commonwealth, and the centre would remain on standby for the next 12 months.
Also set to end on June 16 are the NT's virus exclusion zones, rules for high-risk settings, such as aged-care facilities, and safety measures for businesses, with further details set to be released over the next week.
Major-event and cruise-ship limits and lock-in areas will also cease, along with the controversial vaccine mandate that required most workers to have three jabs.
Ms Fyles said workplaces would now be able to implement their own vaccination policies and decide whether they allowed staff who had lost their jobs for failing to comply with the mandate to return.
Darwin's COVID-19 vaccination and testing centres will close on June 30.
"Territorians have had two years of hard grind,'' Ms Fyles said.
"They have done things we never thought we would have to do ... and we did lose lives. Tragically 52 Territorians were taken from us."
Virus reporting and isolation rules stay, along with face mask requirements for some settings.
The Chief Health Officer will also retain the power to issue directions for up to two years, including mandating masks and vaccines, under recently passed legislation.
"We must remember as we step forward the threat does remain,'' Ms Fyles said.
"There are people dying across the country and the world each day, but we are moving into a world where we are living with COVID.
"This really is the new normal. COVID-19 is a part of our lives."
The territory's high vaccination rate and the slowing spread of the virus and its prevalence in the community are behind the decision.
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