From 1961 to 1970, under the name of the Department of Plant Protection and Quarantine, the department was sometimes merged with the Crop Production Division of the Ministry of Agriculture. After some time, it was separated again into the Department of Plant Protection and Quarantine.
During the first ten years of establishment, the Department of Plant Protection and Quarantine faced unstable office locations: initially, the headquarters was at 2 Ngoc Ha, within the Ministry of Agriculture's area.
During the period of U.S. imperialist bombing, the department was evacuated to Ha Tay, and in 1969, it returned to work at 135 Nam Dong Street, now 149 Ho Dac Di, Dong Da District, Hanoi.
In its early years, the Department had only a few departments to assist the Department Head: the Direction Department, the Plant Quarantine Department, the General Department, and the Administrative Management Department. To timely direct the work of plant protection and quarantine, regional plant protection stations and inter-provincial plant quarantine departments under the department were established in 1966, such as the Northwest, Viet Bac, Northeast, Coastal, and Zone 4 Plant Protection Stations, as well as plant quarantine departments in Hai Phong, Hanoi, Lao Cai, Lang Son, and Zone 4. In various localities, plant protection departments were part of the crop cultivation departments of the provincial Department of Agriculture.
From 1971 to 1981,the department was merged with the Institute of Plant Protection, but later separated again to form the Department of Plant Protection, within the General Department of Crop Production.
From 1981 to 1975,when the country was divided into two regions, the department's office was evacuated to Tay Tuu (Tu Liem, Hanoi). It returned to 135 Nam Dong in 1973 and has remained at the current location since then.
From 1976 to 1991, after the reunification of the country, the Ministry assigned the Department of Plant Protection to manage the national plant protection work. Immediately after reunification, plant quarantine stations were established in Da Nang, Ho Chi Minh City, Central Plant Protection Station, and Southern Plant Protection Station.
From 1992 to 2002, , in 1993, the Law on Plant Protection and Quarantine was published, marking the highest legal document for the plant protection industry since its establishment. Based on Decree 92/CP from the government, the plant protection system was consolidated from central to local levels. In 1992, the plant protection material company separated from the department. In the same year, the crop cultivation division moved to the Department of Agricultural Extension. In 1993, the sterilization company separated from the department, and the department's name reverted to the Department of Plant Protection, assuming its specialist regulatory role as per the Law. In 2003, in accordance with Decree No. 86/2003/ND-CP issued on August 7, 2003, the Ministry of Agriculture and Rural Development issued Decision No. 88/2003/BNN-QD on September 4, 2003, outlining the department's functions, tasks, powers, and organizational structure.
By 2004, the department's structure included seven departments: Plant Protection, Plant Quarantine, Pesticide Management, Administration-Organization, Planning (including international cooperation), Finance, and Inspection-Legal Affairs, with a representative office in Ho Chi Minh City and 17 units under the department.
On July 30, 2004, the Ministry of Agriculture and Rural Development issued a decision to establish the Plant Quarantine Center Post-Import II, and renamed the Center for Analysis, Appraisal, and Plant Quarantine Testing as the Plant Quarantine Appraisal Center.
In 2008, the Minister of Agriculture and Rural Development issued Decision No. 17/2008/BNN-QD on January 28, 2008, detailing the functions, tasks, powers, and organizational structure of the Department of Plant Protection. The department's structure then consisted of the leadership board and 8 departments: Plant Protection, Plant Quarantine, Forest Pest Management, Pesticide Management, Planning, Finance, Inspection-Legal Affairs, Office, with 18 subordinate units.
In 2011, the Minister issued Decision No. 434/QD-BNN-TCCB on March 10, 2011, establishing the Food Safety & Environment Management Department within the Department of Plant Protection.
In 2012, the Minister issued Decision No. 697/QD-BNN-TCCB on March 30, 2012, establishing the Inspection and Legal Affairs Department within the Department of Plant Protection.
In 2017, the Minister issued Decision No. 928/BNN-QD-TCCB on March 24, 2017, establishing the department's organizational structure, including a leadership board, 10 advisory departments, and regional plant quarantine centers.
In 2024, the Minister issued Decision No. 4188/BNN-QD-TCCB on October 11, 2023, detailing the functions, tasks, powers, and organizational structure of the Department of Plant Protection.