Officers have detained three suspects and are searching for a fourth over the deadly incident, a spokesman for the national police told AFP.
The fight erupted at dawn in front of a restaurant that was hosting the wedding in Torrejón de Ardoz, some 25 kilometres (16 miles) northeast of Madrid.
After the dispute, a car rammed into wedding guests and then sped away.
“When we arrived on the scene, we found four people had died of multiple fractures,” said Carlos Polo, head of Madrid emergency services.
Four others who were injured have been transferred to hospital for treatment, he said.
The vehicle suspected of having carried out the attack was spotted 50 kilometres from the scene of the accident and its three occupants arrested, police said.
Local media identified the trio as a father and his two children.
Police said they were searching for a fourth suspect alleged to have been involved.