Guthrie is a city in Todd County, Kentucky, in the United States. The population was 1,415 according to the 2020 census.

The present location of Guthrie was the site of the Pondy Woods stagecoach stop in the 1840s; the community around it may have also been called State Line for a time, from the nearby Tennessee state line.  The town was named for former Representative James Guthrie, the president of the Louisville and Nashville Railroad at its founding in 1867. Guthrie was formally incorporated by the Kentucky Assembly in 1876. The town is also the birthplace of the first United States Poet Laureate Robert Penn Warren.