Born at Fort Dix, New Jersey, Thompson attended John F. Kennedy High School in Riviera Beach, Florida (now Suncoast Community High School). He received a Bachelor of Business Administration from Florida A&M University in 1971 and an MBA from MIT Sloan School of Management in 1983. A large advocate of outdoor conservation, he works largely with Ducks Unlimited.
Before moving on to become Symantec's CEO in 1999, Thompson's 28-year career with IBM Corporation included senior executive positions in sales, marketing and software development, and lastly as general manager of IBM Americas as well as membership in the company’s Worldwide Management Council.
In September 2002, Thompson was appointed to the National Infrastructure Advisory Committee (NIAC) which makes recommendations regarding the security of the critical infrastructure of the United States.
Thompson purchased a 20 percent share of the Golden State Warriors NBA team in 2005 along with three other Silicon Valley businessmen under the umbrella of the Bay Area Basketball Partners, L.L.C.
In April 2006, Forbes published a list of the most highly compensated CEOs. Thompson was ranked #8 with a total compensation of US$71.84 million.
Thompson was a strong supporter of Barack Obama's campaign during the 2008 election cycle. In January 2009, news sources reported that President-elect Obama was considering Thompson to fill the Secretary of Commerce post in the Obama administration. Ultimately, Senator Judd Gregg was chosen for the post but withdrew his name on February 12. Thompson again remained a potential candidate until the successful appointment of Gary Locke.
Speaker of the House Nancy Pelosi appointed Thompson to the Financial Crisis Inquiry Commission in 2009.
In 2010, Thompson was recognized for his commitment to education in Silicon Valley at the Silicon Valley Education Foundation's 2010 Pioneers & Purpose event. He received the Pioneer Business Leader award, which is awarded to individuals who have achieved outstanding accomplishments in Business and education.
On February 4, 2014, Thompson was appointed as chairman of Microsoft, succeeding Bill Gates. Prior to being named chairman, Thompson had been a member of the Microsoft Board for two years. He stated that he joined the board because he had "admired Microsoft for many, many, many years". Thompson said he considered Microsoft to be "one of the true, iconic companies in our country".