Crews have been at the Beechmere supported living complex in Rolls Avenue since 16:30 BST on Thursday.
Cheshire Fire Service said the apartments in Crewe had sustained "significant damage".
Residents have also been evacuated from houses in nearby Railton Avenue overnight due to the fire and smoke.
Cheshire Police confirmed the residents had been placed in temporary accommodation and others taken to an emergency rest centre.
Cheshire Fire Service said crews from across the county and Staffordshire are at the scene.
The spokesperson added that 16 fire engines and two aerial platforms were being used to tackle the blaze.
A number of road closures remain in place, including at Minshull New Road, Bradfield Road, Parkers Road and Underwood Lane.
Members of the public are being advised to avoid the area.
North West Ambulance Service was at the scene on Thursday evening and has been assessing the situation.,
The retirement apartments house some 150 people over the age of 65.
Any relatives with concerns have been advised to contact Cheshire Police.