The trio were awarded for a series of "ground breaking discoveries concerning embryonic stem cells and DNA recombination in mammals", according to the Nobel jury.
Both Capecchi and Smithies are US citizens but were not born in America. Capecchi was born in Italy and Smithies, in Britain.
The winners of the Nobel Prize for Physics will be announced Tuesday, to be followed by those for Chemistry Wednesday, Literature Thursday, Peace Friday and Economics next Monday.
The annual Nobel Prizes are usually announced in October and are handed out Dec 10, the anniversary of the death in 1896 of Alfred Nobel, a Swedish industrialist and the inventor of dynamite.
Nobel died childless and dedicated his vast fortune to create "prizes to those, who, during the preceding year, shall have conferred the greatest benefit on mankind".
The prizes have been awarded since 1901. Each prize consists of a medal, a personal diploma and a cash award of 10 million Swedish kronor (over $1.50 million).