Chaos broke out after a protest in the port city against the coronavirus restrictions and government plans to restrict access for unvaccinated people to some venues.
Dozens of people were arrested and seven people were injured in total, including police officers, during the night-time rampage on one of Rotterdam's main shopping streets.
The Netherlands went back into Western Europe's first partial lockdown of the winter last Saturday with at least three weeks of curbs on restaurants, shops and sports.
"Warning shots were fired several times. At one point the situation became so dangerous that officers felt compelled to shoot at targets," police said.
Rotterdam mayor Ahmed Aboutaleb described the riots as an "orgy of violence".
"The police have felt the need to draw a police weapon in the end to defend themselves," he told reporters.
Police said in a statement that the demonstration that started on the Coolsingel street "has resulted in riots. Fires have been set in several places. Fireworks were set off and police fired several warning shots."
"There are injuries related to the fired shots," they added. They did not give a number but public broadcaster NOS said two people were hurt.
Dutch media said several hundred protesters shouted slogans including "freedom", then threw stones at police and firefighters and set fire to several electric scooters.