"These thrust Tibetans into such depths of suffering and hardship that they literally experienced hell on earth. The immediate result of these campaigns was the deaths of hundreds of thousands of Tibetans."
Lamenting that Tibetan culture and identity were "nearing extinction", he said "even today Tibetans in Tibet live in constant fear ... regarded like criminals, deserving to be put to death".
The 74-year-old leader of the Tibetan government-in-exile also repeated a demand for "legitimate and meaningful autonomy" for Tibet, not independence from China.
Beijing brands the Dalai Lama a "splittist" bent on separating Tibet from China, but he said that Tibetans were seeking "an arrangement that would enable Tibetans to live within the framework of the People's Republic of China".
The Dalai Lama fled from Lhasa on March 10, 1959 after Chinese forces crushed an uprising against its rule in the Himalayan region.
Tibet's government-in-exile says that more than 80,000 people died between March and October of 1959 alone and that at least 200 more were killed last year when Chinese security forces clamped down on protests marking the anniversary.
China denies that it used violence to stop anniversary commemorations last year, saying instead that rioters were responsible for nearly two dozen deaths.
In his speech on Tuesday, the Dalai Lama called for the use of peaceful means of achieving the Tibetan cause.
"I have no doubt that the justice of Tibetan cause will prevail if we continue to tread a path of truth and non-violence," he said.
In the run-up to the anniversary, China has ramped up security inside Tibet and in Tibetan areas of neighbouring Chinese provinces.
Chinese forces have set up checkpoints to seal off the region while foreign tourists as well as journalists were told to leave several weeks ago.
The government has also apparently stopped internet and text-messaging services - which helped spread word of last year's protests – in parts of the region.
Outside of China, however, Tibetan exiles and their supporters have been holding rallies calling for an end to Chinese rule over the region.
In Australia, scuffles broke out between protesters and police outside the Chinese embassy in Australia.
Police said four of about 300 protesters who marched from parliament in Canberra to the nearby embassy were arrested after they broke through fencing demarcating a designated protest area.
The four men were later released without charge, police said.
In Kathmandu, the Nepalese capital, police said some 150 Tibetan exiles staged a protest marking the uprising's anniversary.
Protesters, including monks and school children, screamed "Stop the killing in Tibet" and "Long live the Dalai Lama," as they scuffled with riot police inside a monastery.
Around six protesters were bundled into a waiting police truck, the AFP news agency reported, but were released minutes later.
In the US, on Monday, hundreds of Tibetan exiles and their supporters rallied in front of the White House in Washington DC, with cries of "Free Tibet" and anti-China slogans before marching to the Chinese embassy.