Isaac Monroe Cline was born in 1864 in Monroe County, Tennessee. At the age of 16 he attended Hiwassee College, where he studied mathematics, chemistry, physics, Latin, and Greek. Although he entertained the ideas of becoming a preacher and a lawyer, he eagerly accepted an opportunity to join the U.S. weather service when he was recommended for the position by the president of Hiwassee College. In 1882, he began training with the Army Signal Corps, then the parent organization of the United States weather service. The Signal Corps was a cavalry organization that trained its members in horsemanship and inflicted a military discipline on its aspiring meteorologists.

When Isaac Cline entered the weather service, it was beset by scandal and by the contempt of the general public for its inability to forecast the weather. The Signal Corps' chief financial manager had been convicted one year previously for embezzling a quarter million dollars and had since escaped from prison. Worse, the Signal Corps' track record for predicting storms was very poor, competing in newspapers with the forecasts of astrologers. Forecasting techniques were so primitive that the service was hesitant to allow its junior members to forecast weather publicly, for fear they would be wrong. In this time of corruption and disrepute for the weather service, Cline was honored with a post in the weather station in Little Rock, Arkansas, where he earned a medical degree from the University of Arkansas in his spare time.

He was promoted in 1885 to take over the weather station in Fort Concho, Texas. He subsequently was transferred from Fort Concho to the Abilene station, where he married his wife, Cora May Bellew. In 1889 he transferred to Galveston, Texas, where he was the meteorologist during the great storm of 1900 that devastated the city.

Cline earned acclaim for river forecasting as well as weather forecasting. He published a book, Tropical Cyclones which grew out of his experience with hurricanes and other tidal phenomena.

He retired from his official duties in the Weather Bureau in 1935.