Koch attended the Deerfield Academy prep school in Massachusetts, graduating in 1959. He went on to the Massachusetts Institute of Technology (MIT), earning both a bachelor's (1962) and a master's degree (1963) in chemical engineering. He is a member of the Beta Theta Pi Fraternity. Koch played basketball at MIT, averaging 21 points per game at MIT over three years, a school record. He also held the single-game scoring record of 41 points from 1962 until 2009, when it was eclipsed by Jimmy Bartolotta.

In 1970, Koch joined Koch Industries under his brother Charles, to work as a technical-services manager. He founded the company’s New York office and in 1979 he became the President of his own division, Koch Engineering, renamed Chemical Technology Group. In 1985, Koch Industries was sued by bill Koch and Frederick R. Koch for the first time in a long series of lawsuits about ownership, that lasted until 2001. As of 2010, David Koch owned 42 percent of Koch Industries, as does his brother Charles. He holds 4 U.S patents.

Koch gave his own Vice Presidential campaign $100,000 a month after being chosen as Ed Clark's running mate. "We'd like to abolish the Federal Elections Commission and all the limits on campaign spending anyway," Koch said in 1980. When asked why he ran, he replied: "Lord knows I didn't need a job, but I believe in what the Libertarians are saying. I suppose if they hadn't come along, I could have been a big Republican from Wichita. But hell—everybody from Kansas is a Republican."

In 1984, Koch founded, served as Chairman of the board of Directors of, and donated to the free-market Citizens for a Sound Economy (CSE). richard H. Fink served as its first President. Koch is Chairman of the Board and gave initial funding to the Americans for Prosperity Foundation and to a related advocacy organization, Americans for Prosperity. A Koch Industries spokesperson issued a press release stating “No funding has been provided by Koch companies, the Koch foundations, or Charles Koch or David Koch specifically to support the tea parties.” Koch was the top initial funder of the Americans for Prosperity Foundation at $850,000. Koch said that he sympathizes with the Tea Party movement, but denies directly supporting it, stating: "I’ve never been to a tea party event. No one representing the tea party has ever even approached me."

In 1992, Koch was diagnosed with prostate cancer. He underwent radiation, surgery, and hormone therapy, but the cancer returned every time. Koch has said he believes his experience with cancer has encouraged him to fund medical research. Koch says that his biggest contributions go toward a "moon shot" campaign to finding the cure for cancer, according to his profile on Forbes. Between 1998 and 2012, Koch contributed at least $395 million to medical research causes and institutions.

In 2006, he gave $20 million to Johns Hopkins University School of Medicine in Baltimore for cancer research. The building he financed was named the David H. Koch Cancer Research Building .

In 2007, he contributed $100 million to the Massachusetts Institute of Technology for the construction of a new 350,000-square-foot (33,000 m) research and Technology facility to serve as the home of the David H. Koch Institute for Integrative Cancer Research, Since joining the MIT Corporation in 1988, Koch has given a total of $185 million to MIT. $15 million to New York-Presbyterian Hospital Weill Cornell Medical Center and $30 million to the Memorial Sloan–Kettering Cancer Center in New York.

In July 2008, Koch pledged $100 million over 10 years to renovate the New York State Theater in the Lincoln Center for the Performing Arts, now named in his honor and pledged $10 million to renovate fountains outside the Metropolitan Museum of Art.

Kimberly O. Dennis, President and chief executive officer of the Searle Freedom Trust, said in 2010 that the Kochs are acting against their economic interest in promoting "getting government out of the Business of running the economy. If they were truly interested in protecting their profits, they wouldn’t be spending so much to shrink government; they’d be looking for a bigger slice of the pie for themselves. Their funding is devoted to promoting free-market capitalism, not crony capitalism."

Time included Charles and David Koch among the Time 100 of 2011, for their involvement in supporting the Tea Party movement and the criticism they received from liberals.

In February 2012, during the Wisconsin gubernatorial recall election, Koch said of Wisconsin governor Scott Walker, "We're helping him, as we should. We've gotten pretty good at this over the years. We've spent a lot of money in Wisconsin. We're going to spend more," and said that by "we" he meant Americans for Prosperity.

Koch considers himself a social liberal, supporting women's right to choose, gay rights, same-sex marriage and stem-cell research. He opposes the war on drugs. Koch supports policies that promote individual liberty and free market principles, and supports reduced government spending. Koch supports a non-interventionist foreign policy; "Pursuing a very aggressive foreign policy," he says, "is an extremely expensive endeavor for the U.S. government. The cost of maintaining a huge military force abroad is gigantic. It's so big it puts a severe strain on the U.S. economy, creating economic hardships here at home." Koch opposed the Iraq War, saying that the war has "cost a lot of money and it's taken so many American lives", and "I question whether that was the right thing to do. In hindsight that looks like it was not a good policy". In an impromptu interview with the blog ThinkProgress, he was quoted as saying he would like the new Republican Congress to "cut the hell out of spending, balance the budget, reduce regulations, and support Business." He is against the Patient Protection and Affordable Care Act and the Dodd–Frank Wall Street Reform and Consumer Protection Act. He is skeptical about anthropogenic global warming. He has said a warmer planet would be good because "Earth will be able to support enormously more people because a far greater land area will be available to produce food".

In July 2015 David Koch and his brother were commended by both President Obama and Activist Anthony Van Jones for their bipartisan efforts to reform the prison system in the United States. For nearly ten years the Kochs have been advocating for several reforms within the Criminal justice system which include, reducing recidivism rates, simplifying the employment process for the rehabilitated, and defending private property from government seizures through asset forfeiture. Allying with groups such as the ACLU, the Center for American Progress, Families Against Mandatory Minimums, the Coalition for Public Safety, and the MacArthur Foundation, the Kochs maintain the current prison system unfairly targets low-income and minority communities at the expense of the public budget.