They say the religious sect, founded a century ago in the United States, threatens lives by pressuring sick people into refusing medical aid. Prosecutors say the group also creates rifts between family members with its practice of not celebrating national holidays.
There are an estimated 10,000 Jehovah's Witnesses in Moscow, and more than 250,000 across the country.
Jehovah's Witnesses claim no one is forced to practice their religion and stress that any ban on the group would defy the Russian Constitution and the European Convention on Human Rights.
"If we lose and we are banned and liquidated, other parts of Russia will follow suit, so for us the stakes are extraordinarily high," said Jehovah's Witness Judah Schroeder.
A judgment against the group could lead to the banning of other sects, including the Mormon Church and the Seventh-Day Adventists. Orthodox Church threatened?
Jehovah's Witnesses say the trial is not about theology, but turf.
"It is clear that the Russian Orthodox Church is concerned about the growth of non-traditional religions that have come into Russia in the past few years," Schroeder said.
The Orthodox Church supports the new law, which enshrines it as the country's main religious group. Metropolitan Kirill, one of the Orthodox Church's Moscow leaders, accused Jehovah's Witnesses on Tuesday of "intruding on the people's spiritual world and exerting psychological pressure," the Interfax news agency reported.
"There have been cases when this pseudo-religious manipulation of the public contained a material factor, that is, human souls were virtually bought or dragged by other dirty methods into the orbit of the teaching," he said.
If banned, Jehovah's Witnesses would be forced underground, unable to hold public services or rent property -- conditions similar to what the group experienced under communism.
Correspondent Steve Harrigan and The Associated Press contributed to this report.