Mao was regarded as the founder of modern bridge engineering. Mao's long and productive career included designing two of the most famous modern bridges in China, the Qiantang River Bridge near Hangzhou, and the Wuhan Yangtze River Bridge at Wuhan.
The Qiantang River Bridge designed with his guidance is the first dual-purpose road-and-railway bridge designed and built by the Chinese themselves. He also participated in the construction of China's first modern bridge – Wuhan Yangtze River Bridge. During the construction of Wuhan Yangtze River Bridge, Mao Yisheng served as chairman of the Technical Advisory Committee composed of more than 20 foreign and Chinese bridge experts, and solved 14 difficult problems relating to bridge construction.
He also led the structural design of the Great Hall of the People in Beijing.