Measures include allowing US citizens to use credit cards in Cuba and for US businesses to export some technologies.
Americans will be able to take home up to $100 (£66) in alcohol and tobacco from Cuba. Correspondents say it means the US ban on Cuban cigars is over.
The move implements last month’s agreement to re-establish ties severed since 1961.
Although the latest moves put a large dent in the US trade embargo against Cuba, only Congress can lift it completely.
Earlier this week, US officials said Cuba had completed the release of 53 political prisoners agreed as part of the historic deal.
“Today’s announcement takes us one step closer to replacing out-of-date policies that were not working and puts in place a policy that helps promote political and economic freedom for the Cuban people,” said US Treasury Secretary Jacob Lew in a statement.
White House press secretary Josh Earnest said the changes would “immediately enable the American people to provide more resources to empower the Cuban population to become less dependent upon the state-driven economy”.
While it still bans ordinary tourism, the new regulations will allow US citizens to travel to Cuba for any of a dozen specific reasons without first obtaining a special licence from the government.
US credit and debit cards can be used there and there will be no more limits on how much money US citizens can spend in Cuba each day.
About 170,000 authorised US travellers went to Cuba last year, according to the US Department of Commerce.
US firms will also find it easier to export mobile phones and software to Cuba, as well as provide internet services there.
Cuba currently has one of the lowest internet penetration rates in the world – estimated at about 5% by the White House.
A change in the regulations will also allow US investments in some small businesses and agricultural operations.
The thaw in relations between the two countries was announced last month in simultaneous televised speeches by President Barack Obama and his Cuban counterpart, Raul Castro.
Later this month, US Assistant Secretary of State Roberta Jacobson will lead a delegation to Cuba to discuss migration issues.
They will be the first high-level talks since the easing of relations was announced.
President Obama used his executive powers to ease the embargo, defying hardline critics. Analysts say Congress is unlikely to agree to lift the embargo completely any time soon.
Cuban-American Republican Senator Marco Rubio said Mr Obama’s policy would harm ordinary Cubans.
“This is a windfall for the Castro regime that will be used to fund its repression against Cubans,” he said in a statement.