Walker also founded the hardware integration manufacturing company Marinchip. Among other things, Marinchip pioneered the translation of numerous computer language compilers to Intel platforms.
In 1982, John Walker and 12 other programmers pooled US$59,000 to start Autodesk (AutoCAD), and began working on several computer applications. The first completed was AutoCAD, a software application for computer-aided design (CAD) and drafting. AutoCAD had begun life as InteractCAD, written by programmer Michael Riddle in a proprietary language. Walker and Riddle rewrote the program, and established a profit-sharing agreement for any product derived from InteractCAD. Walker subsequently paid Riddle US$10 million for all the rights.
By mid-1986, the company had grown to 255 employees with annual sales of over $40 million. That year, Walker resigned as chairman and president of the company, continuing to work as a programmer. In 1989, Walker's book, The Autodesk File, was published. It describes his experiences at Autodesk, based around internal documents (particularly email) of the company.
Walker moved to Switzerland in 1991. By 1994, when he resigned from the company, it was the sixth-largest personal computer software company in the world, primarily from the sales of AutoCAD. Walker owned about $45 million of stock in Autodesk at the time.
He publishes on his personal domain, fourmilab.ch, designed to be a play on Fermilab. On his website, Walker publishes about his personal projects, including a hardware random number generator called HotBits along with software that he writes and freely distributes such as his Earth and Moon viewer. 
In popular culture
Walker's interest in artificial life prompted him to hire Rudy Rucker, a mathematician and science fiction author, for work on cellular automata software. Rudy later drew from his experience at Autodesk in Silicon Valley for his novel The Hacker and the Ants, in which one of the characters is loosely based on John Walker.
- Walker, John (August 21, 1996). "The Animal Episode". Fourmilab. Retrieved March 20, 2012.
- Parikka, Jussi (2007). Digital Contagions: A Media Archaeology of Computer Viruses. Peter Lang. pp. 41, 239–40. ISBN 9780820488370.
- Stern, Zack (May 2008). "White Paper: The Evolution of Viruses". Maximum PC. Retrieved March 20, 2012.
- Markoff, John (1999). "Saying Goodbye, Good Riddance To Silicon Valley". The New York Times. ISSN 0362-4331. Retrieved 2018-03-20.
- Markoff, John (1994-04-28). "COMPANY NEWS; Autodesk Founder Saddles Up and Leaves". The New York Times. ISSN 0362-4331. Retrieved 2017-08-22.
- McCarty, John R. (May 30, 1986). "Micro-miracle: Autodesk has 'image' of success". The Pittsburgh Press. Retrieved March 20, 2018.
- Zachary, G. Pascal (1992-05-29). "'Theocracy of Hackers' Rules Autodesk Inc., A Strangely Run Firm". Wall Street Journal. ISSN 0099-9660. Retrieved 2018-03-20.
- Markoff, John (April 28, 1994). "Autodesk Founder Saddles Up and Leaves". The New York Times. Retrieved March 20, 2012.
- "Telling the Story Behind Autodesk". New Straits Times. November 2, 1989. Retrieved March 20, 2012.
- Walker, John (1989). The Autodesk File: Bits of History, Words of Experience. New Riders Pub. ISBN 9780934035637.
- Walker, John. "HotBits: Genuine random numbers, generated by radioactive decay". fourmilab.ch. Retrieved March 30, 2006.
- Walker, John. "Earth and Moon Viewer". fourmilab.ch. Retrieved March 30, 2006.