As president, Theodore Roosevelt used an expansive definition of executive power to pursue monopolies, or trusts, that he saw as injurious to the public welfare. This led to some high-profile showdowns with powerful businessmen, such as his successful lawsuit against the Northern Securities Company, a railroad trust controlled by plutocrat and financier J. P. Morgan. As a result of this case and a handful of others (as well as Roosevelt's talent for self-promotion and image creation), he became known as the "trust-busting" President. But in truth, Roosevelt generally preferred to regulate the trusts, which, in many cases, he saw as beneficial to economic growth. He encouraged state legislation and signed federal laws (like the Hepburn Act) that placed regulations on big corporations. He also sought to empower the Interstate Commerce Commission to enforce these regulations. When he ran for reelection in 1912 on the so-called "Bull Moose" ticket, he doubled down on this program of government control of the trusts, which he saw as part of a generally beneficial centralization of the economy. Over time, in short, he moved to a position of increased government control over economic concerns, including the trusts.

Woodrow Wilson generally sought to promote competition in the economy, eschewing, at least in rhetoric, the program of centralization endorsed by Roosevelt. But if anything, he was more hostile to the trusts than Roosevelt. He did not, for example, distinguish between "good" trusts and those run by "malefactors of great wealth" condemned by Roosevelt. He signed into law the Clayton Anti-trust Act, which limited the ability of large corporations to merge in ways that would lead to monopolies. This was part of his program announced in 1912 and styled the "New Freedom," a significant rhetorical departure from the "New Nationalism" espoused by Roosevelt. Wilson was suspicious of all trusts, especially inasmuch as they limited the competition he believed was at the heart of economic success.

Woodrow Wilson and Theodore Roosevelt had different views on how to regulate big business. Theodore Roosevelt believed that the government and big businesses could exist and work together. Roosevelt believed the government must intervene and regulate businesses when business acted in ways that only benefitted its own interests while hurting the public’s interests. This was done with the Northern Securities Company. The creation of the company nearly caused an economic crisis. Roosevelt took the company to court and won as the company had to be broken up because it violated antitrust laws. This concept of treating everybody equally was known as the Square Deal.

Wilson, on the other hand, believed big businesses had to be tightly regulated by the government. He wanted to see monopolies eliminated. As part of his New Freedom program, the Clayton Antitrust Act was passed, and the Federal Trade Commission was created. Both of these actions gave the government more power in dealing with big businesses. Both Wilson and Roosevelt had ideas on how to deal with big businesses.

A major difference in their respective approaches has to do with how they attacked monopolies.  Roosevelt is known for the fact that he did not try to attack all monopolies.  He believed that there were both good monopolies and bad monopolies that were greedy and exploitative.  Roosevelt tried to go after the bad ones while leaving the good ones alone.  By contrast, Wilson did not try to differentiate between good and bad monopolies.  Instead, he pushed for laws that specified certain types of actions (such as price discrimination or interlocking directorates for large corporations) were illegal in all cases.  This was very different from Roosevelt's idea of taking the monopolies on a case-by-case basis.