The two scientists, Andrew Fire, 47, of Stanford University and Craig Mello, 45, of the University of Massachusetts Medical School -- among the youngest to receive the prize, discovered that a double strand of Ribonucleic acid, or RNA, the genetic messenger of the cell, can "silence" specific genes in a process called RNA interference, Reuters reported.
The ability to control gene activity is a breakthrough, especially in the treatments for cancer, HIV and heart disease.
The scientists published their work on gene control in 1998.
The pair expressed surprise on being awarded the honor only eight years since the discovery. The Nobel committee usually waits decades before awarding the most prestigious prize in science.
Both scientists told Reuters that their research builds on the work of many other researchers such as those in the Human Genome Project, which identified genes.
Their research helped shed new light on a complicated process that has confused researchers for years, said Nobel committee member Erna Moller.
The winners were awarded the prize, which includes $1.4 million, by the Karolinska Institute in Stockholm.
"I had an inkling that it might be possible, but I am only 45 so I thought it might happen in 10 or 20 years or so," said Mello, according to the Associated Press.
He said the two might give some of the money to charity.