Captain Lee Joon-seok, 69, and three crew members are being accused of “homicide through willful negligence”. The others face lesser charges.
The trial will focus on Lee Joon-seok’s escape from the sinking ferry while hundreds of passengers remained trapped inside.
Most of the victims of the April disaster were school students, and many of their relatives are at the court.
If convicted, Lee Joon-seok and three crew members could be handed the death penalty, but observers say it is extremely unlikely it would be carried out.
Eleven other crew are being tried on lesser charges of criminal negligence and maritime law violations.
A nationwide manhunt is also under way for fugitive Korean businessman Yoo Byung-Eun, who is believed to own the Chonghaejin Marine company that ran the sunken ferry.
Yoo Byung-Eun’s daughter, Yoo Som-Na, 47, was detained in May at her home in Paris under an international arrest warrant.
Authorities are also searching for his eldest son, Yoo Dae-Kyun, offering a $100,000 for information leading to his arrest.
Yoo Byung-Eun is wanted for questioning on possible charges of embezzlement and criminal negligence.
Prosecutors have offered a $500,000 cash reward for information leading to Yoo Byung-Eun ‘s arrest.
Analysts say there are concerns that the crew will be unable to receive a fair trial in the district court in the south-western city of Gwangju.
The Sewol ferry disaster caused an outpouring of public anger, and there have been calls for severe punishment for the crew.
President Park Geun-hye condemned the conduct of some of the crew of the ferry, calling it “akin to murder”.
The confirmed death toll from the South Korea ferry disaster has reached 292, with 12 passengers still missing.
Prosecutors say the ferry owner ignored safety warnings and allowed the ship to be overloaded.
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