On June 2, 2021, the Fortune 500 list of the United States was released simultaneously with the English website worldwide. Overall, affected by the global epidemic, the threshold for this year's list has dropped from US$5.66 billion last year to US$5.37 billion. The total revenue of all 500 companies on the list also fell slightly to about US$13.8 trillion, a decrease of 3.15% from last year. The total revenue of the companies on the list is equivalent to two-thirds of the US GDP that year.

In 2020, the total profit of these largest American companies was US$858.6 billion, a sharp decrease of 29.8% compared with last year, the largest drop since 2009. On this year's list, Walmart topped the list for the ninth consecutive year, and Amazon remained in second place. Thanks to the hot sales of iPhone 12, Apple's revenue increased by 5.5%, and its ranking rose to third place.

In terms of profitability, Apple's profit increased by 3.9% compared with the previous year, returning to the top of the profit list; while Microsoft's profit increased by 12.8%, ranking second. The technology and financial industries are still the most profitable industries. Among the top ten most profitable companies, 9 are from these two industries. In contrast, 108 companies on the list did not make a profit this year; compared with last year, there were 48 more companies. ExxonMobil suffered an annual loss for the first time in 40 years and became the company with the largest loss on the list, with a loss of more than 22.4 billion US dollars. Occidental Petroleum, a company in the same industry, ranked second on the loss list, with a loss of more than 14.8 billion US dollars. Delta Airlines and Boeing also lost more than 10 billion US dollars.