The top court observed that development of nuclear energy is important for India and allowing the plant is in larger public interest.
It said all expert bodies were of unanimous opinion that adequate safety measures had been taken.
A clutch of petitions had challenged a Madras High Court order in August last year that, while asking India's nuclear watchdog to ensure that necessary safeguards were complied with, gave the go-ahead for the loading of fuel in the plant.
The petitioners had opposed the plant's operationalisation arguing many of the 17 additional safety measures prescribed by a government task force had not been put in place. The Centre has said 15 of those mostly enhanced safety features have been implemented and the rest will be in due course.
The judgement comes close on the heels of the detection of four faulty valves in the first reactor unit of the plant which were later replaced. Some Russian officials were also arrested recently over alleged corruption in sourcing sub-standard materials from some Russian nuclear plants.
Locals and activists have been agitating for the last two years against the plant, demanding closure of the plant. Idinthakarai, which is just three kilometres away from the plant complex, has served as the Ground Zero of the protests. Fishermen, who form the majority of the population staying in the plant's vicinity, are worried that the nuclear plant will adversely affect marine life and hence, their livelihood.
The People's Movement Against Nuclear Energy (PMANE), which has been spearheading the anti-Kudankulam campaign, has cited the Fukushima disaster in Japan, triggered by a massive tsunami, to draw parallels about the dangers of a nuclear plant. It has also raised various questions pertaining to the disposal of nuclear waste, besides other issues linked to the plant.
D Udayakumar, the coordinator for PMANE, told NDTV that "people cannot be murdered in the name of sustainable development" and that the "Supreme Court is silent on liability and waste management issues."
The Nuclear Power Corporation of India Ltd (NPCIL), which operates the plant, too insists that the plant is safe and is "fully equipped to withstand" Fukushima-type incidents.
Tamil Nadu Chief Minister J Jayalalithaa, who initially supported the cause of the anti-Kudankulam movement, later did a U-turn - after two committees gave their nod - citing that the project could bring relief to the state which is reeling under a severe power shortage.
The power project is being set up in Kudankulam, around 650 kilometres south of Chennai, with two Russian-made, 1,000-MW nuclear reactors.