Sussex Police confirmed its officers were assisting East Sussex Fire and Rescue Service with the incident.
A spokesman said: “Police are responding to a report of part of Lewes Castle collapsing on to buildings in Castle Ditch Lane, Lewes.
“Fire service colleagues have requested the assistance of search dogs and a drone having been alerted at 12.22pm on Monday (November 11).
“It is not known at this time if anyone is trapped as a result.”
East Sussex Fire and Rescue Service said a multi-agency meeting was currently underway to make an assessment of the search and rescue operation.
A spokesman said: “Emergency crews remain at the scene of an incident at Lewes Castle.
“A search of the area is not yet underway, due to the instability of the Old Coach House. ESFRS is working with other emergency services to gain a safe access.
“Currently, there are no reports of anyone missing, or any casualties.
“The area of wall collapse is not part of the main castle and not immediately accessible by the public. This is expected to be a protracted incident, involving a multi-agency search and rescue operation.
“East Sussex Fire & Rescue Service were mobilised to Lewes Castle, following reports of a wall collapse in the Old Coach House.
“Lewes firefighters were initially mobilised at 12.22 today (November 11), and called further assistance from Sussex Police, SECamb, HART, Building Control, the Red Cross and specialist teams, including both Kent and West Sussex Urban Search & Rescue.
“Members of the public are being asked to avoid the area, while the incident is on-going, as there are expected to be a high number of emergency appliances involved in this multi-agency search and rescue operation.
“Firefighters are working alongside other emergency services to check the area to ensure that no-one needs rescuing.”
A spokesman for SECAmb said: “We had a call at 1.20pm to Ditch Lane, Lewes, to reports that a wall near Lewes Castle had collapsed. Ambulance crews are on scene, including our Hazardous Response Teams, alongside the police and fire service.”
An eyewitness near the scene said five police cars, a dog unit, and a number of ambulance vehicles were parked in Lewes High Street, between Popes Passage and Castle Gate. They said Popes Passage had been cordoned off by police.