Klarman was born on May 21, 1957 in New York City. When he was six, he moved to the Mt. Washington area of Baltimore, Maryland near the Pimlico Race Course. His father was a public health economist at Johns Hopkins University and his mother was a psychiatric social worker His parents divorced shortly after their moving to Baltimore.

Klarman attended Cornell University in Ithaca, New York, and was interested in majoring in mathematics but instead chose to pursue economics. He graduated magna cum laude in economics with a minor in history in 1979.. He was a member of the Delta Chi fraternity. In the summer of his junior year, he interned at the Mutual Shares fund and was introduced to Max Heine and Michael Price. After graduating from college, he went back to the company to work for 18 months before deciding to go to business school. He went on to attend Harvard Business School where he was a Baker Scholar and was classmates with Jeffrey Immelt, Steve Burke, Stephen Mandel, James Long, and Jamie Dimon.

After graduating from business school in 1982, he founded The Baupost Group with Harvard Professor William J. Poorvu and partners Howard H. Stevenson, Jordan Baruch and Isaac Auerbach. The name is an acronym based on the founders’ names (the name was decided on before Klarman joined the project). Poorvu asked Klarman and his associates to manage some money he had raised from the selling of his share in a local television station and the fund was started with US$27 million in start up capital. His starting salary was $35,000 a year, considered low to alternative job offers, and he later recalled that the other founders “were taking a big risk on a relatively inexperienced person.” Early on in his investment career, he used to badger Goldman Sachs salesmen with so many questions regarding their options and thoughts on the markets that they were afraid to pick up the phone if they saw that Baupost was calling.

Klarman typically keeps a low profile, rarely speaking in public or granting interviews. He lives in Chestnut Hill, Massachusetts with his wife, Beth Schultz Klarman, whom he met on a Boston Harbor cruise in 1982; they have three children. His brother, Michael Klarman, is a professor at Harvard Law School.

Klarman has written many annual letters to shareholders but has kept a limited role in writing articles, op-eds or books. In 1991, Klarman published his only book, Margin of Safety, Risk Averse Investing Strategies for the Thoughtful Investor (1991), a reflection of value investing found in his hedge fund. In the book, he outlines the various issues with retail investing, and critiques small time investors getting into the market purely using metrics such as share price momentum and losing money in the long run. He issues that this is speculation and at times gambling, and should be discouraged in the market place. The book asserts that more people should follow the principles of value investing or people who invest in stocks that trade below their underlying value so as to purchase them at a discount.

In February 2008, Klarman was alerted that a London-based hedge fund, Peloton Partners, were forced to liquidate more than a billion dollars worth of their assets, he decided to open up his fund to new investors subsequently raising $4 billion in capital, mainly from large foundations and Ivy League endowments. He believed that there was serious market opportunity for value investors in the coming months and after the collapse of AIG and Lehman Brothers, he invested heavily in the equity markets, sometimes buying $100 million in stocks and other assets per day. While the market was down due to the aftermath of the crisis he purchased many distressed securities and bonds. By early 2009, after JPMorgan Chase acquired Washington Mutual as a part of their deal with the United States Department of the Treasury, Sallie Mae bonds were returning double digit figures for Baupost. Overall, Klarman’s bond position appreciated 25%, however, during the financial crisis, his fund returned -7% to -13%. Although many hedge funds faced negative returns and low performance during the crisis and its aftermath, Klarman saw increased equity positions and described it as a “fortuitous time” for the fund’s capital gains. The same year he would go on to buy a minority share in the Boston Red Sox, via a stake in Ed Eskandarian.

In 2008, he was inducted into Institutional Investors Alpha’s Hedge Fund Manager Hall of Fame along with Alfred Jones, Bruce Kovner, David Swensen, George Soros, Jack Nash, James Simons, Julian Roberston, Kenneth Griffin, Leon Levy, Louis Bacon, Michael Steinhardt, Paul Tudor Jones and Steven A. Cohen.

He edited the 6th edition of Benjamin Graham and David Dodd’s Security Analysis in 2008.

In 2009, Klarman began buying distressed credits in the wake of the financial crisis of 2007–2008. He purchased the bonds of CIT Group, a financial holding company based in New York City at 65 cents on the dollar with a yield rate of 15%. After the company went into prepared bankruptcy, as Baupost began lending it money via a loan, Carl Icahn gave a loan of $6 billion to the CIT Group but backed out of the deal a week later. This caused the bonds to speed into prepared bankruptcy and gave the Baupost group securities valued at 80 cents to the dollar for their debt in CIT Group. Shortly after the CIT deal was finalized, Klarman amassed a stake in a new bio-tech company called FacetBiotech, at an average cost of $9 a share. At the time, FacetBiotech had $17 a share in net cash. Klarman noted that when stocks are spun off of their larger parent companies they become “cheap and ignored.” When Biogen eventually tried a hostile takeover of the company bidding up the price to $14 a share, Abbott Laboratories asked for a $27 per share settlement for acquisition. Klarman’s fund finished that year up +27%.

In a 2011 interview with Charlie Rose, Klarman states he does not use a Bloomberg Terminal (an almost ubiquitous computer system used in major U.S. financial companies to track market data). Klarman stated due to his long-term strategy he is mostly uninterested in daily price fluctuations.

In 2013, Klarman donated the lead capital to fund the $61 million building at Cornell University named the Seth ’79 and Beth Klarman Humanities Building, more simply known as Klarman Hall. A year later, he donated money to Harvard Business School to construct a “conference center/auditorium and performance space,” named Klarman Hall. It opened in 2018. In 2019, Cornell University announced that Klarman had donated significant funds to help establish a new postdoctoral fellowship program at the school, the Klarman Fellowships.

He makes unusual investments, buying unpopular assets while they are undervalued, using complex derivatives, and buying put options. During his first years running Baupost, he made it a point to only invest in companies that were not widely accepted by the Wall Street community; he stressed managing risk and using the margin of safety. He is a very conservative investor, and often holds a significant amount of cash in his investment portfolios, sometimes in excess of 50% of the total. Despite his unconventional strategies, he has consistently achieved high returns. Klarman looks for companies that are traded at a discount (so he can assume shares with a margin of safety). Klarman and his fund usually go “bargain hunting,” when companies are distressed or face low growth or declining years. In 2015, when energy stocks were declining, his firm “started looking for deals.” According to Institutional Investor, “[Klarman] has succeeded by deftly exploiting under-valued markets whether they are in equities, junk bonds, bankruptcies, foreign bonds or real estate.”

As of 2016, the fund had US$31 billion in assets under management.

Klarman has donated to both Democratic and Republican groups and candidates while being registered an Independent politician; however, since the election of Donald Trump in 2016, he has donated almost exclusively to Democrats. He has also given extensively to philanthropic causes through the Klarman Family Foundation, which he runs with his wife. The foundation has $700 million in assets as of 2018 and gave away $40 million in 2016. It focuses on pro-democracy initiatives, such as supporting groups that protect journalists, fight against bigotry, and advocate for LGBT rights.

In the 2016 presidential election, he gave the maximum donation of $5,400 to Hillary Clinton’s campaign, stating that “Donald Trump is completely unqualified for the highest office in the land.”

Although Klarman gave $2.9 million to Republican candidates in 2016, he told The New York Times in September 2018, “One of the reasons I’m willing to come out of my shell and talk to you is because I think democracy is at stake, and maybe I’ll be able to convince some other people of that, and get them to support Democrats in 2018.” Klarman, who was previously one of the biggest donors to the Republican Party in New England, told the Times in September, 2018, that he had already contributed almost $5 million to nearly 150 candidates, including Representative Joe Kennedy III, Senate candidate Representative Beto O’Rourke and Senator Kirsten Gillibrand. Klarman is a registered Independent who reasoned, “We need to turn the House and Senate as a check on Donald Trump and his runaway presidency.” He commented that he feels “betrayed” by “spineless” Republicans who have been “profiles in cowardice,” and believes the only option is to “act as a check and balance.”