Ross was born on November 28, 1937, in Weehawken, New Jersey, and grew up in suburban New Jersey. His Father, Wilbur Louis Ross Sr., was a Lawyer who later became a judge, and his mother, Agnes (née O'Neill), was a school Teacher.

In the late 1970s, Ross began his career at the New York City office of N M Rothschild & Sons, where he ran the bankruptcy-restructuring advisory practice.

In the 1980s, Donald Trump was in financial trouble. His three casinos in Atlantic City were under foreclosure threat from lenders. Ross, who was then the senior managing Director of Rothschild Inc., represented Investors in the casino. Along with Carl Icahn, Ross convinced bondholders to strike a deal with Trump that allowed Trump to keep control of the casinos.

In 1999, Ross was awarded the Order of Industrial Service Merit medal by South Korea's President Kim Dae Jung for his assistance during the 1998 Korean financial crisis.

Ross' private equity fund, WL Ross & Company, was created in April 2000. He had started a $200 million fund at Rothschild to invest in distressed assets. As the U.S. bubble began to burst, he decided he wanted to invest more and advise less. In 2000, the 62-year-old banker raised $450 million to buy out the fund from Rothschild and make further Investments in distressed assets. The new firm was named WL Ross & Co. In 2003 investment committee was composed of David H. Storper, David L. Wax, Stephen J. Toy, and Pamela K. Wilson, a J.P. Morgan & Co. veteran. In 2006 Ross sold WL Ross & Co. to Invesco, then Amvescap. WL Ross operates as a subsidiary of Invesco.

In 2002, Ross founded International Steel Group after purchasing the assets of several bankrupt steel companies. Ross had support from the local steelworkers union, negotiating a deal with them to "save" Pennsylvania's steel industry. Leo Gerard, international President of the United Steelworkers union stated about Ross that "he was open and accessible and candid and honest and he put a lot of money back into the mills, so literally tens of thousands of jobs were saved." Ross sold International Steel Group to Mittal Steel Company for $4.5 billion, half in cash and half in stock, in April 2005.

Ross married Judith Nodine in 1961. They divorced in 1995. Together, they had two children, Jessica and Amanda. In 1995, he married his second wife, New York Lt. Governor Betsy McCaughey. They divorced in 2000. On October 9, 2004, Ross married his third wife, Hilary Geary, a society Writer for Quest magazine.

The Sago Mine disaster was a 2006 explosion in a coal mine indirectly owned by International Coal Group that led to the deaths of 12 miners. Federal investigators said a lightning strike was the most likely ignition source for the blast. Following the disaster, the New York Post's Roddy Boyd reported that the mine had 12 roof collapses in 2005, and that the U.S. Department of Labor data showed 208 citations for safety violations in that same period, including 21 times for build-up of toxic gasses. Miners and their families accused Ross of ignoring safety violations. Ross defended his company's management of the mine. Arch Coal purchased International Coal Group for $3.4 billion in 2011.

Ross has been on the Board of Directors of Navigator Holdings since March 2012.

On the subject of foreign trade, Ross has said: "I am not anti-trade. I am pro-trade, but I'm pro-sensible trade. [Being anti-trade] is a disadvantage of the American worker and the American Manufacturing community." Ross has also said that the government "should provide access to our markets to those countries who play fair, play by the rules and give everybody a fair chance to compete. Those who do not should not get away with it – they should be punished." Initially in favor of the Trans-Pacific Partnership, Ross has said that after examining the agreement, he found it was "not consistent with what was advertised."

Ross began working with Ireland and Irish-American causes starting in 2011 with an investment in the then-struggling Bank of Ireland. In recognition for his efforts on November 6, 2014 Ross was awarded the American Irish Historical Society Gold Medal at the Waldorf Astoria Hotel, New York. The medal is awarded to "individuals who make an especially meritorious contribution to Irish American Life".

Ross was awarded the medal of the Order of the Rising Sun, Gold and Silver Star by Japanese Ambassador Sumio Kusaka on behalf of the Japanese government at Kusaka's New York residence on February 2, 2015. This was in recognition for strengthening the bonds between Japan and the US (including his Service as Chairman of the Board of New York's Japan Society, which had begun in 2010 after being on its board of Directors since 2005), his work to promote and strengthen the Japanese economy, and his relief efforts after the 2011 Tōhoku earthquake and tsunami.

On November 24, 2016, the Associated Press reported that Trump would nominate Ross to become United States Secretary of Commerce. The Trump transition team confirmed this on November 30 and on February 27, 2017, he was confirmed by the United States Senate in a 72–27 vote. Ross took office at the age of 79, making him the oldest first-time cabinet appointee in U.S. history. The previous record-holder was Philip Klutznick, who took office at the age of 72. Ross stated in an interview with CNBC that his priorities as Commerce Secretary is to be reducing the United States' trade deficit, and working with private companies on infrastructure.

In November 2017, Paradise Papers reporting found that after becoming commerce secretary, Ross retained Investments in Navigator Holdings, a shipping company he once controlled which transports petrochemicals for Russian gas and petrochemicals company Sibur. Sibur has American sanctions against it for its close ties to Russian Oligarchs Leonid Mikhelson and Gennady Timchenko, and President Vladimir Putin's son-in-law Kirill Shamalov. He had failed to clearly disclose these ties to Russian interests during his confirmation hearings. While his confirmation was pending, Ross promised in a letter to the Office of Congressional Ethics to cut ties "with more than 80 financial entities in which he has interests". This letter played a key role in securing his confirmation. However, according to the leaked documents, while he did divest some holdings, he did not disclose the full extent of those he retained. Senator Richard Blumenthal accused Ross of misleading the Senate Committee on Commerce and the American people by giving the impression that he had divested entirely from Navigator and by not disclosing Navigator's ties to the Kremlin. Blumenthal called for an investigation by the inspector general of the Commerce Department. Ross denied wrongdoing and said that he had declared his financial interests in early 2017 prior to his confirmation hearing. Speaking about his financial ties to Navigator, Ross said the media was making "a lot more out of it than it deserves" and "There is nothing wrong with it. The fact that it happens to be called a Russian company doesn't mean there is any evil in it."

In 2017, Ross said that a trade deal with the United Kingdom was a low priority for the Trump administration; however, he outlined possible terms and blamed the European Union for making a deal with the United Kingdom more difficult. Under Ross, the Department of Commerce has recommended to President Donald Trump an increase of tariffs in aluminum and steel imports. President Donald Trump declared on March 1, 2018 a 25% tariff on steel and a 10% tariff on aluminum imports.