Prime Minister Narendra Modi launched the Covid-19 vaccine programme, which aims to vaccinate more than 1.3 billion people against Covid.
He paid tribute to front-line workers who will be the first to receive jabs.
India has recorded the second-highest number of Covid-19 infections in the world after the United States.
Millions of doses of two approved vaccines – Covishield and Covaxin – were shipped across the country in the days leading up to the start of the drive.
“We are launching the world’s biggest vaccination drive and it shows the world our capability,” Mr Modi, said, addressing the country on Saturday morning.
He added that India was well prepared to vaccinate its population with the help of an app, which would help the government track the drive and ensure that nobody was left out.
Mr Modi spoke at length about doctors, nurses and other front-line workers “who showed us the light” in “dark times”.
“They stayed away from their families to serve humanity. And hundreds of them never went home. They gave their life to save others. And that is why the first jabs are being given to healthcare workers – this is our way of paying respect to them.”
Mr Modi also appealed to people to continue adhering to Covid-19 safety protocols like wearing masks and following social distancing. He said the country cannot afford to be complacent as vaccinating the entire population will take time.
He also urged people not to believe any “propaganda and rumours about the safety of the vaccines”.
“I want to tell people that the approval to these vaccines was given only after scientists and experts were satisfied about its safety,” he said.
An estimated 10 million health workers will be vaccinated in the first round, followed by policemen, soldiers, municipal and other front-line workers.
Next in line will be people aged over 50 and anyone under 50 with serious underlying health conditions. India’s electoral rolls, which contain details of some 900 million voters, will be used to identify eligible recipients.
The government plans to vaccinate 300 million people by early August. This will happen in state-run health care centres, schools, colleges, community halls, municipal offices and wedding halls.
Several hospitals across India are also giving the first doses of the vaccine.