She was born in Chappaqua, New York to Colonel Nicholas Smith, a New York City lawyer and diplomat, and Ida Lillian Greeley, who died when she was two. Her grandfather was Horace Greeley.

She worked at Joseph Pulitzer's papers and developed a distinctive style to her human interest stories and interviews. She covered home front activities during World War I and was an advocate for women's suffrage. She was known for securing interviews with people of high status and for her unflinching questions and willingness to address controversial subjects. Mary Heaton Vorse said, "I pity the unwary who are interviewed by Nixola Greeley-Smith."

She married Andrew Watres Ford, a newspaper editor. They had no children and she died of acute appendicitis in 1919.