The break in a 24-inch pipe near the city's Campus Martius Park could take all day to repair, the Detroit News reported.
Darryl Latimer, deputy director of the water and sewer department, said the basements of many of the buildings without water could become flooded.
The break was the latest in a series of leaks to plague the city.
A break in a 30-inch line last week forced utility crews to work in gushing water, deep snow and frigid temperatures.
Earlier this month, a 16-inch main broke on the city's east side, creating a small lake that stranded three cars and a minivan.