Cole became a Presbyterian missionary under the auspices of the
Board of Foreign Missions in 1875, and sailed for southeast Asia that year. She was principal of girls' school at the
Chiang Mai Mission Station from 1878 to 1883. She worked with her old classmate, Mary Margaretta Campbell, at Chiang Mai, until Campbell died by drowning in 1881. After a furlough in the United States in 1883 and 1884, known as the Wang Lang Girls' School, beginning in 1885. She took a leave of absence in India in 1899, "made necessary by seven years of work so severe and exhausting that few could have borne the strain". In 1892, and in 1904 and 1905, she lectured about her work in the United States. Cole was an energetic head of the school; she launched a student magazine in 1892, wrote plays, worked on writing a "new geography of Siam", invested in land and modern buildings to expand the school, and renamed the school as the Wattana Wittaya Academy, a name that projected ideas of progress and prosperity. Cole retired in 1923, Cole was an early and active member of the
Siam Society. Her students included Sangwan Talaphat—the future Princess Mother
Srinagarindra—who studied English with Cole before pursuing further education in the United States and meeting Prince
Mahidol Adulyadej. Novelist and fellow missionary Margaret Landon knew Cole well, and consulted Cole's letters home to her sister in the United States in her research for writing
Anna and the King of Siam. == Personal life and legacy ==