Wai-Kai Chen's youth was troubled by the Sino-Japanese War of 1937–1945 followed by the civil war between the Nationalist and Communist forces. Born into an intellectual family, he had a twin brother Wai-Fah, an older brother Hollis, an older sister Eileen, a younger sister Helena, and a younger brother Wai-Sun. The family was on the Nationalist side. In 1949 Wai-Kai Chen's maiden aunt went with Wai-Sun and Helena went to Taiwan. Some time later, Wai-Kai, Wai-Fah, and Hollis made a harrowing and adventurous escape to Taiwan. In Taipei, Wai-Kai and Wai-Fah entered formal education as sophomores in the Junior High School of Taiwan Normal University. In the 1950s Wai-Kai Chen went to the United States to study electrical engineering. In September 1962 in White Plains, New York, he married Shirley Chen (the sister of his friend Stanley S. Chen).

Wai-Kai Chen is a professor and head emeritus of the Department of Electrical Engineering and Computer Science at the University of Illinois at Chicago. He has extensive experience in education and industry and is very active professionally in the fields of circuits and systems. He was Editor-in-Chief of the IEEE Transactions on Circuits and Systems, Series I and II, President of the IEEE Circuits and Systems Society, and the Founding Editor and Editor-in-Chief of the Journal of Circuits, Systems, and Computers. He is the recipient of the Golden Jubilee Medal, the Education Award, the Meritorious Service Award from the IEEE Circuits and Systems Society, and the Third Millennium Medal from the IEEE. Professor Chen is a fellow of the IEEE and the American Association for the Advancement of Science.