It will be closed for up to three months with patients instead being cared for 24 miles away at Wansbeck General Hospital in Ashington.
The works are required to help ensure the building is properly ventilated, has en-suite facilities and areas that can be used to better manage the ongoing pandemic.
It follows a review by infection prevention control experts who recommended some urgent changes.
One of the measures is moving the inpatient ward to the ground floor to improve accessibility.
The work is expected to be completed by mid-February and will also see improvements take place to outpatient facilities.
Outpatient appointments and other services are continuing as normal during the building works.
Marion Dickson, Northumbria Healthcare NHS Foundation Trust executive director of nursing, midwifery and allied health professionals, said: “We understand this may be difficult for people and we apologise for the inconvenience this may cause patients and relatives.
"This decision has not been taken lightly and is a direct result of a number of infection outbreaks that have caused us some concern.
“After a review by our infection prevention control experts, it’s clear that work needs to urgently take place to improve the ventilation, create some en-suite facilities and improve the environment for patients and staff.
"Part of these improvements will include moving the ward to the ground floor making it more accessible.
“I’d like to thank the patients and families involved for their understanding as well as the hard-working staff involved in their care.”
Alnwick Infirmary has provided healthcare services to the community and surrounding district for more than 100 years.
Ward 1 provides specialist rehabilitation and support for inpatients. The multi-disciplinary ward team cares for patients who may be recovering from an illness or operation, often following a spell in another hospital, and help them to recover, get back on their feet and gain confidence.
It was also closed in summer 2020 for around four weeks for an upgrade to the lift, power supply and air system to address ongoing issues.