In his address to the 15-member UN Security Council on Tuesday, Antonio Guterres described the Chad-Sudan situation as probably the "largest and most complex humanitarian problem on the globe".
"Today, violence and impunity - never completely in check - are again everyday occurrences in Darfur," he said. "Humanitarian workers are regularly cut off from the displaced and those they are trying to help."
Guterres said armed rebels had recently attacked the village of Guereda in eastern Chad, where the UN refugee agency (UNHCR) was caring for some 25,000 Sudanese refugees.
He added that averting a catastrophe would require "bold measures" and the full involvement of the African Union and the UN.
Chad and Sudan have long traded accusations, each side claiming the other is supporting its insurgents. In December, the Chadian government declared "a state of belligerence" between itself and Sudan following a deadly border attack Chad blamed on the Sudanese government.
The two governments are currently engaged in talks to ease tensions along their shared border.
An estimated 200,000 refugees from strife-torn Darfur are being housed in camps in eastern Chad. According to UNHCR, nearly 800 Sudanese refugees have arrived in eastern Chad since the beginning of the year, fleeing continuing insecurity in the neighbouring West Darfur region of Sudan.
"The newly arrived Sudanese refugees all cite the current deterioration of security in Darfur - including attacks by the Janjaweed [alleged Khartoum-backed militia] and a recent rise of tensions between Chad and Sudan - as the main reasons for fleeing," UNHCR spokesperson Ron Redmond told reporters on Tuesday.
"Security has worsened in West Darfur in recent months, resulting in a reduction in the number of aid workers operating in the area," he added, noting that the new arrivals were receiving help in Gaga camp, east of Abeche, the main town in eastern Chad.
"If we fail, if there is no physical protection for those in need of aid, the risk is much a greater calamity than what we have seen so far," Guterres said.