Malini Parthasarathy, the first woman editor of The Hindu daily, put in her papers on Tuesday.
The 138-year-old daily is one of the largest and oldest newspapers in the country.
Parthasarathy, who became the editor in 2013, is the daily's second editor to quit in a short time.
In 2013, Siddharth Varadarajan quit as the editor.
In an internal communication, employees were informed that the nomination and remuneration committee has accepted Parthasarathy's resignation.
The committee also decided that the daily's national editor Suresh Nambath will manage the day-to-day affairs and the editorial operations until an editor is appointed.
According to the communication, Parthasarathy will continue as the wholetime director of Kasturi & Sons Ltd., the company that owns The Hindu.
Responding to a tweet, Parthasarathy tweeted that she has no new adventure in the line.
It was during her tenure that The Hindu launched its Mumbai edition a couple of months ago.
Parthasarathy and Kasturi & Sons chairman N. Ram were not available for comments despite several attempts by IANS.
