Born in Berlin, Germany to Jewish parents, he escaped Nazi Germany in 1935, emigrating with his family to the United States. He started studying mathematics in 1941 in the US, but his studies were interrupted by the war, during which he served in the military. Around 1952 he worked on analog computers, and helped create a digital computer for Wayne State University. In 1956 he worked for General Electric on ERMA, a computer system that introduced the use of the magnetically-encoded fonts imprinted on the bottom border of checks. This allowed automated check processing via Magnetic Ink Character Recognition, and in 1964 took a position at MIT.
In 1962 (or 1966 according to ELIZA), he published a comparatively simple program called ELIZA, named after the ingenue in George Bernard Shaw's Pygmalion, which demonstrated natural language processing by engaging humans into a conversation resembling that with an empathic psychologist. Weizenbaum modeled its conversational style after Carl Rogers, who introduced the use of open-ended questions to encourage patients to communicate more effectively with therapists. The program applied pattern matching rules to the human's statements to figure out its replies. (Programs like this are now called chatterbots.) It is considered the forerunner of thinking machines. Weizenbaum was shocked that his program was taken seriously by many users, who would open their hearts to it. He started to think philosophically about the implications of Artificial Intelligence and later became one of its leading critics.
His influential 1976 book Computer Power and Human Reason displays his ambivalence towards computer technology and lays out his case: while Artificial Intelligence may be possible, we should never allow computers to make important decisions because computers will always lack human qualities such as compassion and wisdom. This he saw as a consequence of their not having been raised in the emotional environment of a human family.
Weizenbaum was the creator of the SLIP programming language.
In 1996, Weizenbaum moved to Berlin and lived in the vicinity of his childhood neighborhood.
A German documentary film on Weizenbaum was released in 2007 and later dubbed in English.
Until his death he was Chairman of the Scientific Council at the Institute of Electronic Business in Berlin. In addition to working at MIT, Weizenbaum held academic appointments at Harvard, Stanford and the University of Bremen, and other universities. Weizenbaum was reportedly buried at the Jewish Cemetery in Berlin. A memorial serivce was held in Berlin on March 18, 2008.