The death toll from Wednesday's undersea quake of 7.6 magnitude was expected to rise further after rescuers dig through the rubble in heavily populated towns of Sumatra Island. The second, 6.8-magnitude quake damaged additional buildings on Thursday.
"This is a high-scale disaster," Health Minister Siti Fadilah Supari said.
Padang, a coastal city of 900,000 and capital of West Sumatra province, became the immediate focus of relief workers.
At least 500 buildings in Padang collapsed or were badly damaged in the Wednesday evening quake, which also set off fires, said Disaster Management Agency spokesman Priyadi Kardono.
A total of 467 people were confirmed dead and 421 seriously injured, said Tugiyo Bisri of the Social Affairs Ministry's crisis center. He said 376 deaths occurred in Padang, with rest of the deaths in four surrounding districts.
At least 80 people were missing at the 5-story Ambacang hotel in downtown Padang, said Indra, a paramedic who uses only one name. Rescuers, working in heavy rain, found two survivors and nine bodies in the hotel's rubble.
Terrified residents who spent a restless night were jolted by the fresh tremor on Thursday morning.
The US Geological Survey said the inland quake with a preliminary magnitude of 6.8 hit about 150 miles (240 kilometers) south of Padang at a depth of just under 20 miles (24 kilometers).
The second quake reportedly damaged 30 houses in Jambi, another Sumatran town. It was not yet clear if there were injuries, said Jambi Mayor Hasfiah, who uses only one name, like many Indonesians.
Collapsed or seriously damaged buildings in Padang included hospitals, mosques, a school and a mall. TVOne network footage showed heavy equipment breaking through layers of cement in search of more than 30 students it said were missing from the school where they were taking after-school classes.
Parents of missing students stayed up all night, waiting for signs of life under the rubble.
"My daughter's face keeps appearing in my eyes ... my mind. I cannot sleep, I'm waiting here to see her again," a woman, who identified herself only as Imelda, told TVOne, tears rolling down her face. She said her 12-year-old daughter Yolanda was in school to take science lessons.
"She is a good daughter and very smart. I really love her. Please God help her. I hope rescuers, everybody... can help her out of here. Please!" she said.
An unidentified boy told TVOne that he escaped from the top floor just as the three-story school crumpled. He said he was taking math lessons while many others were taking science courses.
Wednesday's temblor severed roads and cut off power and communications to Padang. Thousands fled in panic, fearing a tsunami. The shaking was so intense that people crouched or sat on the street in fear.
Children screamed as an exodus of thousands of frantic residents fled in cars and motorbikes, honking horns.
The quake was felt hundreds of miles (kilometers) away in Malaysia and Singapore, causing buildings there to sway.
The extent of damage in surrounding areas was still unclear due to poor communications. Indonesia sits on a major geological fault zone and is frequently hit by earthquakes.
More than 3,000 people were killed in the last big earthquake in 2006 that hit Yogyakarta, a major city on the main island of Java.
The latest quakes came in the wake of a killer tsunami Tuesday that hit islands in the South Pacific, killing at least 120 people. Geologists said the two events were not related.
The Padang quakes were along the same fault line that spawned the 2004 Asian tsunami that killed 230,000 people in a dozen nations.
Padang's mayor appealed for assistance on Indonesian radio station el-Shinta.
"We are overwhelmed with victims and ... lack of clean water, electricity and telecommunications," Mayor Fauzi Bahar said. "We really need help. We call on people to come to Padang to evacuate bodies and help the injured."
Thousands were believed trapped throughout the province, said Rustam Pakaya, head of the health ministry's crisis center.
The shaking felled trees and crushed cars in Padang. A foot could be seen sticking out from one pile of rubble. At daybreak, residents used their bare hands to search for survivors, pulling at the wreckage and tossing it away piece by piece.
The loss of telephone service deepened the worries of those outside the stricken area.
Hospitals struggled to treat the injured as their relatives hovered nearby.
Indonesia's government announced $10 million in emergency response aid and medical teams and military planes were being dispatched to set up field hospitals and distribute tents, medicine and food rations.
Local television reported more than two dozen landslides in the province. Some blocked roads, causing miles-long traffic jams of cars and trucks.