Čmilytė-Nielsen competed in the Women's World Chess Championship for the first time in 2000, when she reached the third round. In 2004 she was defeated in the quarterfinals by former Women's World Champion Maia Chiburdanidze. In 2006, Čmilytė-Nielsen reached the semifinals and lost to the eventual runner-up, Alisa Galliamova. In 2008 and 2010 she was eliminated in the second round, while in 2010 and 2015 she went out in round three.