Born in Berlin to Jewish parents, Weizenbaum had emigrated in 1936 to the United States. After having contributed to the development of the first analog computers and participating in the design of the first digital computers for banking applications, Weizenbaum in 1963 took a position at the Massachussetts Institute of Technology (MIT); from 1970 he was professor for computer science. Among his major achievements were studies over the SLIP programming language and research on basic software technologies which today are in widespread use such as garbage collection algorithms.

One of his most influential works was the development of the natural language processor ELIZA which is said to be one of the early breakthroughs for Artificial Intelligence. In this context, he developed a program simulating a conversation between a physician and a patient.

Shocked over the fact that many test series participants were unable to determine they in fact were communicating with a computer and openly divulged most intimate details of their life, Weizenbaum developed a more critical and reserved posture towards information technologies and turned into an inconvenient admonisher. He co-founded the Computer Professionals for Social Responsibility group. Until his death, he also was Chairman of the Scientific Institute of Electronic Business in Berlin.

In 1996, Weizenbaum moved to Berlin. On March 5, he died in consequence of apoplexy.