The Syrian Observatory for Human Rights said the blast in the city of Qamishli killed 10 members of the Kurdish forces, called the Asayish, and six civilians.
"A suicide bomber in a vehicle targeted the Asayish's local headquarters in Qamishli," said Rami Abdel Rahman, head of the British-based Observatory.
ISIS claimed the attack in an online statement, saying a suicide bomber had used a "water tanker rigged with explosives to infiltrate an Asayish command base".
Syrian Kurdish militia have been some of the most successful forces fighting ISIS in northern parts of the country.
Suicide Bomber Kills 16, Wounds 50 in Northeast Syria
The terrorist group has targeted Qamishli and other Kurdish bastions with suicide operations in the past.
Abdel Rahman described Wednesday's explosion as "massive" and said at least 14 civilians had been wounded.
The charred wreckage of several vehicles was seen at the site of the blast in the industrial district of Qamishli, a majority-Kurdish city in Syria's northeast Hasakeh province.
Syria's state news agency SANA reported 50 people were wounded.
Arin Shekhmos, a local journalist in Qamishli, said the blast could be heard throughout the city.
"I wasn't close, but I could hear it from where I was," Shekhmos told AFP by telephone shortly after visiting the blast site.
"There is a lot of destruction -- the buildings on at least two streets have been completely destroyed," he said.