A health ministry official said the unnamed man, who was in his thirties while working at the plant following the 2011 crisis, has leukaemia. He is now 41, local media reported.
The announcement will likely further inflame widespread public opposition to nuclear power, and could frustrate efforts to resettle evacuees in communities around the crippled Fukushima plant that have been deemed safe.
It also comes less than a week after the controversial restarting of a second reactor in Japan following the shutdown of all the country's reactors in the wake of the crisis.
The official revealed few details about the man, but said he had worked at a destroyed building that housed one of the plant's crippled reactors.
The man, who wore protective equipment during more than a year spent at Fukushima, will be awarded compensation to pay for his medical costs and lost income, the official said, without elaborating on the amount.
Public broadcaster NHK said about 45,000 people have worked at the Fukushima plant since the accident as part of a massive, multi-billion-dollar cleanup.
There has been hot debate about whether the accident would lead to a rise in cancer among plant employees and those who lived near Fukushima.
"This is a landmark decision from the viewpoint of workers' rights, and it's probably just the tip of the iceberg," Shinzo Kimura, associate professor of radiation and hygiene at Dokkyo Medical University, told AFP.
"This is an alarm bell for that policy," he added.
Plant operator Tokyo Electric Power Co (TEPCO) said it was not "in a position to comment" but expressed sympathy for the man and reiterated a pledge to cut workers' radiation exposure.
No deaths have been directly attributed to the radiation released during the 2011 accident, but it has displaced tens of thousands of people and left large areas uninhabitable, possibly for decades.
