Nikžentaitis received his doctorate from the Lithuanian Historical Institute in 1989. In 1992, he became a founding member of the Research Center for the History of Western Lithuania and Prussia at Klaipeda University (later the Institute of History and Archaeology of the Baltic Region), becoming its first director and later holding the new chair of history. In 1999, he habilitated on Lithuanian society in pre-Christian times. From 2000 to 2008, he headed the Lithuanian Historical Institute and was a professor in Vilnius until 2009. In 2009/2010, he was a fellow of the Alexander von Humboldt Foundation at the Center for the History and Culture of East Central Europe at the University of Leipzig. Since 2009, Nikžentaitis has been a project coordinator and research associate of the Lithuanian Historical Institute. Between 2019 and 2024, he served as director of the Lithuanian Historical Institute for the third time. Since 2024, he has returned to the institute as a project coordinator and research associate.
Nikžentaitis has been Chairman of the Lithuanian Historians' Association since 2004, a member of the board of the Lithuanian-German Forum since 2005, and Chairman of the Lithuanian-Russian Historians' Commission since 2006. Between 2011 and 2024, he was a member of the board of trustees for the Northeast Institute (IKGN e. V.) at the University of Hamburg.
His research focuses on the history of East Central Europe, enemy stereotypes, cultural memory, cultures of remembrance, politics of history, identity change, and the symbolic appropriation of cities.
