Guizhou University was founded in 1902 and has undergone various stages of development, including being named Guizhou University Hall, Provincial Guizhou University, National Guizhou Agricultural and Engineering College, and National Guizhou University. In October 1950, it was officially named Guizhou University. In November 1951, Chairman Mao Zedong personally inscribed the name Guizhou University.

In August 1997, Guizhou University merged with Guizhou Agricultural College and other institutions. In August 2004, it merged with Guizhou University of Technology. Over its 120-plus years of construction and development, Guizhou University has successively become a 211 Project university, a Double First-Class initiative university, and a university jointly constructed by the Ministry of Education and the Guizhou Provincial Government.

In 2021, the Guizhou Provincial Government Work Report explicitly proposed to strengthen Guizhou University for the first time. In November of the same year, the Guizhou Provincial Department of Education and 11 other departments jointly issued the Implementation Plan for Strengthening Guizhou University, aiming to build Guizhou University into a high-level, first-class university that meets the requirements of Chinese characteristics, world-class standards, and Guizhou's needs.

In 2023, the Guizhou Provincial Party Committee and Provincial Government decided to concentrate efforts to strengthen Guizhou University to lead and promote the high-quality development of higher education in Guizhou. The university is also among the first batch of National Demonstration Universities for Party Building Work, the first National Civilized Campus, and a pilot unit for the Ministry of Education's Three Comprehensive Education Reforms.