Seneca is a city in Grant County, Oregon, United States. It is located in the Blue Mountains about 23 miles (37 km) south of Canyon City, on U.S. Route 395, on the edge of the Malheur National Forest. The population was 199 at the 2010 census.

Grant County is one of the 36 counties in the U.S. state of Oregon. As of the 2020 census, the population was 7,233, making it Oregon's fourth-least populous county. The county seat is Canyon City. It is named for President Ulysses S. Grant, who served as an army officer in the Oregon Territory, and at the time of the county's creation was a Union general in the American Civil War.