The group of five high-level government officials, including Moon's top security adviser Chung Eui-yong, intelligence chief Suh Hoon and Vice Unification Minister Chun Hae-sung, boarded a plane at an air base south of Seoul around 1:50 p.m. local time.
The delegation is expected to meet high-level officials in Pyongyang, as well as North Korean leader Kim Jong Un, either on Monday evening or Tuesday afternoon, YTN reported.
Chung, who is leading the delegation, plans to deliver a letter from the South Korean leader.
"I will deliver President Moon Jae-in's sincere and firm resolve to maintain dialogue and improvement in relations between the South and the North, which were fostered during the Pyeongchang Winter Olympics," the security adviser said before his departure, according to Yonhap.
He added that he planned to hold in-depth discussions to address the issue of denuclearizing the Korean Peninsula, as well as dialogue between the United States and North Korea.
After returning to the South on Tuesday afternoon for a debrief, Chung and intelligence chief Suh plan visit the United States to share the outcome of the meeting.
The cross-border visit marks the first of its kind since Moon took office last year.
It is also a reciprocal move following Kim's sister's visit to the South last month during which she handed an invitation to visit the North to the South Korean leader.