In the 1970s, Taiwan's economic development took off, and society's attention to higher education increased day by day. At that time, all well-known universities were located in northern Taiwan, and there was not a single national university in the Kaohsiung-Pingtung area of southern Taiwan. To balance the development of education between the north and the south, the government decided to establish a comprehensive university in the south and named it "National Sun Yat-sen University" in honor of Dr. Sun Yat-sen, the founder of the Republic of China. Enrollment began in the fall of 1980. To further commemorate Dr. Sun Yat-sen's achievements, the Ministry of Education granted the request to date Dr. Sun Yat-sen's birthday of November 12th as the anniversary of the University.

The university places equal emphasis on both teaching and research of Humanities, Sciences, and Engineering. Since 2006, NSYSU has received additional funding from the Ministry of Education (MOE) through the "Aim for the Top University Plan" and "Higher Education Sprout Project" to enhance teaching and research. Outstanding academic achievements exhibited by many departments have landed NSYSU among the world's top universities in many academic rankings.

NSYSU has sister-university agreements with over 250 universities from more than 40 countries around the world. Within these partnerships, the university engage in student exchange, dual degree programs, joint supervision, research collaborations, and joint symposiums. The institution dedicate to create an internationalized campus where thousands of international students come to NSYSU for degree programs, exchange programs, research fellowships, or language learning. The vast array of activities provides ample opportunities for domestic students and international students to interact and bridge their understanding of different cultures.