The occurrence and prevalence of pine wood nematode disease has had a great impact on China’s forestry production and ecological environment, but the quantitative evaluation of the economic losses of this biological disease is lacking from a macro-geographic scale and long-term series perspective. This study establishes a pine wood nematode disease economic loss evaluation index system, covering the loss of natural ecology, landscape aesthetics and economic production, and quantitatively evaluates the economic losses of pine wood nematode disease in mainland China at a provincial level from 1998 to 2017. The results show that the economic losses of the pine wood nematode disease in China showed a fluctuant rising trend from 1998, since 2013, it has entered a full-scale outbreak phase, and since 2015, the economic loss has increased significantly, with a growth rate higher than 40%. The average annual total economic loss is CNY 7.17 billion, of which the direct economic losses is CNY 1.53 billion, and the indirect economic losses is CNY 5.64 billion. The loss of forest material resources, the expenditure of ineffective forest management expenditure and prevention and control expenditure were CNY 817 million, CNY 649 million, and CNY 67 million, respectively. Regulate service value loss, support service value loss and cultural service loss are CNY 3.95 billion, CNY 1.41 billion, CNY 276 million, respectively. East China and South China suffered the most due to pine wood nematode disease, and the economic loss of these regions accounted for 79.9% of the total national economic losses. Among them, Zhejiang Province, Guangdong Province and Jiangsu Province lost CNY 2.14 billion, CNY 1.81 billion, and CNY 1.22 billion, respectively, accounting for 26.8%, 22.7% and 15.3% of the total national economic loss.