Federal authorities deployed thousands of paramilitaries and blocked mobile internet access in the region, while local police who joined them in opposing protesters defying a curfew in Guwahati, in Assam state, opened fire both blank and live rounds.
India's Citizenship Amendment Bill (CAB), passed by the upper house of parliament on Wednesday, allows for the fast-tracking of citizenship applications from religious minorities from three neighbouring countries, but not Muslims.
The two demonstrators killed were among a large group being treated for various wounds at Guwahati Medical College and Hospital, told AFP.
"A few of those people were brought in with bullet injuries. Two of those 21 people have died," said Ramen Talukdar, a doctor at the hospital.
For Islamic groups, the opposition, rights groups and others in India, the new law is part of Prime Minister Narendra Modi's Hindu-nationalist agenda to marginalise India's 200 million Muslims, something he denies.
But many in India's far-flung northeast object because they fear the legislation, which prompted angry exchanges in parliament this week, will give citizenship to Hindu immigrants from Bangladesh.
Five thousand paramilitary troops were deployed in Guwahati, while many roads and highways were blocked to prevent the spread of protests.
Officials said 20 to 30 people have been hurt in the demonstrations in recent days, with vehicles torched and police firing tear gas and charging the crowds with wooded staffs.
Guwahati's top police officer Deepak Kumar was removed from his post and replaced over the outbreak of violence, authorities said.
All train services to Tripura and Assam were suspended and some flights were cancelled. Several cricket and football matches scheduled to take place in Assam were also called off amid the curfew.
Without citing the unrest, Bangladesh home minister Asaduzzaman Khan postponed his Friday visit to northeastern Indian state of Meghalaya, his spokesman Sharif Mahmud Apu told AFP.
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