The river's water level was at about 7.5 metres Wednesday morning, more than four times its normal level.
In 2010, a water level of 7.3 metres resulted in the evacuation of 900 residents from their homes.
A Red Cross reception centre is taking in residents displaced by the flooding.
A release from the City of Sherbrooke late Tuesday night said 24 streets around the city were closed due to floodwaters.
Bishop's University also announced that exams have been cancelled Wednesday for a second day in a row and that its campus is closed to non-residents.