About 50 firefighters remain at the six-storey Wharfside block, on Heritage Way, after the blaze broke out on the top floor at about 04:00 BST on Sunday.
People living in 120 flats were evacuated, with many spending the night in a rescue centre or a local hotel.
All the residents were evacuated, with no injuries reported.
Flames and plumes of smoke could be seen from several miles away.
An investigation has begun into how the fire started.
Steve Sheridan, from Greater Manchester Fire and Rescue Service (GMFRS) said: "It's a total write-off for 50 or 60 flats, which is a sad state of affairs.
"This remains a difficult and complex fire and we do not yet have it surrounded or under control. We have worked immensely hard through the night in difficult conditions but we aren't on top of it yet."
He added: "It is desperately sad for the residents and our thoughts are with them as they watch their homes and all their belongings burn for such a prolonged period of time. We are really trying our best to bring this to a conclusion as soon as possible."
A rescue centre was opened at nearby arts centre The Mill at the Pier by Wigan Council.
Peter Layland, assistant director of housing at Wigan Council, said the affected properties were rented by private landlords.
He said: "We re-housed 50 people last night in a local hotel. We will be talking to them today about arrangements for tonight as well."
Dozens of families have been told they "may never be able to enter their homes again" after a major fire destroyed 60 flats in Wigan.