The East Asian monsoon is the largest periodic airflow on Earth and significantly affects the climate of East Asia. However, considerable controversy exists about the onset timing of the East Asian monsoon. As one of the southern barriers blocking the northward movement of the warm and humid airflow, the Nanling Range has likely recorded key topographic information related to the East Asian monsoon onset and development. We used apatite and zircon (UTh)/He data obtained from the Shaoguan–Guidong horizontal cross-section to reconstruct the two-dimensional (2-D) paleotopography of the Nanling Range on a long-term scale. Four vertical profiles in Shulouqiu, Erjian, Sanfenshi, and Leiwangdian were used to constrain the exhumation history of the Nanling Range. The result revealed the following: 1) The drainage divide began to move from south to north at 80 Ma. At 80 Ma, the south segment of the cross-section reached a peak elevation of ∼3.6 km. The asymmetric topography experienced a rapid elevation (and relief) decrease from 80 Ma to 40–30 Ma. The four vertical profiles also experienced increased cooling and high exhumation rates from 100 Ma to 40–30 Ma. 2) The south segment experienced more rapid exhumation than the north segment from 80 Ma to 40–30 Ma. The rapid exhumation of the south segment during the Late Cretaceous–Paleocene is probably related to the activity of the Nanxiong Fault, and the rapid exhumation of the south segment during the Eocene probably results from the onset of the East Asian Monsoon.