South Korea’s Yonhap news agency cited sources as saying on Sunday that the man, identified only by his surname Kim, was arrested at Pyongyang International Airport on Friday while he was leaving the country.
Kim, aged in his late 50s, was a former professor at China's Yanbian University of Science and Technology and was in North Korea for about a month to discuss relief activities, Yonhap said.
The reason for the arrest is still unclear, with the US State Department saying there was no official confirmation of the arrest.
"We are aware of reports that a US citizen was detained in North Korea," a State Department official said.
“In cases where US citizens are reported to be detained in North Korea, we work with the Swedish embassy, which serves as the United States' Protecting Power in North Korea. Due to privacy considerations, we have no further comment," the official said.
South Korea's National Intelligence Service as well as the unification and foreign ministries said they could not confirm the report.
However, the director of a group called the World North Korea Research Center in Seoul said his sources in Pyongyang had confirmed the arrest.
The news comes at a tense time in relations between Pyongyang and Washington.
US President Donald Trump has urged China to pressure North Korea to curb its nuclear and missile programs.
Last week, US Vice President Mike Pence warned that "all options are on the table" to curb Pyongyang 's nuclear programs amid speculations that the North may be planning a new atomic test.