McAfee was employed as a programmer by NASA’s Institute for Space Studies in New York City from 1968 to 1970. From there he went to Univac as a software designer and later to Xerox as an operating system architect. In 1978 he joined Computer Sciences Corporation as a software consultant. Later, while employed by Lockheed in the 1980s, McAfee received a copy of the Pakistani Brain computer virus and began developing software to combat viruses.
In 1987 McAfee founded McAfee Associates, a computer anti-virus company. He was the first to distribute anti-virus software using the shareware business model. In 1989, he quit Lockheed and began working full-time at McAfee Associates, which he initially operated from his home in Santa Clara, California. The company was incorporated in Delaware in 1992, and McAfee resigned from the company in 1994. Two years after McAfee Associates went public, McAfee sold his remaining stake in the company.
Network Associates was formed in 1997 as a merger of McAfee Associates and Network General. This company later became Network Associates, a name it retained for seven years until it was renamed McAfee. In August 2010, Intel Corporation bought McAfee, maintaining the separate branding, until January 2014, when it announced that McAfee related products will be marketed as Intel Security. McAfee expressed his pleasure at his name no longer being associated with the software.
Other business ventures that he founded included Tribal Voice, which developed one of the first instant messaging programs, PowWow. In 2000, John McAfee invested in and joined the board of directors of Zone Labs, makers of firewall software, prior to its acquisition by Check Point Software in 2003.
In August 2009, The New York Times reported that McAfee’s personal fortune had declined to $4 million from a peak of $100 million, the effect of the global financial crisis and recession on his investments.
Beginning in February 2010, McAfee started a new venture in the field of bacterial quorum sensing. His company QuorumEx has its headquarters in Belize and is working towards producing commercial all natural antibiotics based on anti-quorum sensing technology.
In 2013 McAfee started a new company, Future Tense Central, to produce a secure computer network device called the D-Central.
In February 2014, McAfee announced Cognizant, an application for Android, which displays information about the permissions of other installed applications.
McAfee teaches yoga and has written several books about yoga.
In a 2012 article in Mensa Bulletin, the magazine of American Mensa, he stated that being the developer of the first commercial anti-virus program has made him “the most popular hacking target”, adding “Hackers see hacking me as a badge of honor”. He added that for his own security he has other people buy his computer equipment for him, uses pseudonyms for setting up computers and logging in, and changes his IP address several times a day.