Kai-Fu Lee developed the world's first speaker-independent, continuous speech recognition system as his Ph.D. thesis at Carnegie Mellon. He later worked as an executive, first at Apple, then SGI, Microsoft, and Google.

He became the focus of a 2005 legal dispute between Google and Microsoft, his former employer, due to a one-year non-compete agreement that he signed with Microsoft in 2000 when he became its corporate vice president of interactive services.

One of the most prominent figures in the Chinese internet sector, he was the founding director of Microsoft Research Asia, serving from 1998 to 2000; and president of Google China, serving from July 2005 through September 4, 2009. He created a website, Wǒxuéwǎng (Chinese: 我学网; literally: 'I learn Internet') dedicated to helping young Chinese people achieve in their studies and careers, and his "10 Letters to Chinese College Students" have spread widely on the web. He is one of the most followed micro-bloggers in China, in particular on Sina Weibo, where he has over fifty million followers.

In his book, published in 2018, AI Superpowers: China, Silicon Valley, and the New World Order, Lee describes how China is rapidly moving forward to become the global leader in AI, and may well surpass the United States, because of China's demographics and its amassing of huge data sets. In a 28 September 2018 interview on the PBS Amanpour program, he accentuated that artificial intelligence, with all its capabilities, will never be capable of creativity or empathy. 

Dr. Kai-Fu Lee has a unique perspective on the global technology industry, having worked extensively between the US and China, and has been in artificial intelligence research, development and investment for more than 30 years. He is one of China's top technology investors, undertaking early pioneering work in the field of artificial intelligence and working with multiple US technology giants. 

Lee is the Chairman and CEO of Sinovation Ventures, managing a $1.7 billion dual-currency investment fund. Sinovation is a leading technology-savvy investment firm focusing on developing Chinese high-tech companies. Lee also serves as president of the Sinovation Ventures Artificial Intelligence Institute.

Prior to founding Sinovation in 2009, Lee was the President of Google China. Previously, he held executive positions at Microsoft, SGI and Apple. He is a Fellow of the Institute of Electrical and Electronics Engineers (IEEE), and he was Vice Chairman of the Committee of 100 and named one of the 100 most influential people in the world by TIME Magazine. He is the author of seven best-selling books in Chinese, launching his new book AI Superpowers internationally in fall 2018, and has over 50 million followers on social media.

In the field of artificial intelligence, Lee founded Microsoft Research China, which was named as the hottest research lab by MIT Technology Review. Later renamed Microsoft Research Asia, this institute has trained the great majority of AI leaders in China, including CTOs or AI heads at Baidu, Tencent, Alibaba, Lenovo, Huawei and Haier. While with Apple, Lee led AI projects in speech and natural language, which appeared on Good Morning America on ABC Television and the front page of The Wall Street Journal. He has authored 10 US patents, and more than 100 journal and conference papers.