The visit comes with the longstanding US-Saudi relationship strained by greater American energy independence and last year's international nuclear agreement with Riyadh's regional rival Iran.
The decades-old relationship has been based on an exchange of American security for Saudi oil.
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The prince, King Salman's son, was accompanied by a ministerial delegation including Finance Minister Ibrahim al-Assaf and Commerce and Investment Minister Majid-al-Qasabi.
Prince Mohammed is the main architect of a wide-ranging Vision 2030 plan released in April to diversify the kingdom's economy away from oil.
On the eve of his departure, Prince Mohammed chaired a meeting of the Council for Economic Affairs and Development, the Gulf state's main economic coordination body.
At the heart of Vision 2030 is a plan to float less than 5% of state oil firm Saudi Aramco on the stock market.
The proceeds would become part of the world's largest state investment fund, with $2 trillion in assets.
Profits from the fund would help economic diversification and provide an alternative to oil revenues that have fallen by about half since 2014.
This month, San Francisco-based Uber announced that the Saudi Public Investment Fund has pumped $3.5 billion into the ride-sharing giant.
The move signals a more aggressive global investment presence by the kingdom under its economic restructuring programme. Uber is a smartphone app that connects passengers and drivers around the world.
Prince Mohammed has risen to be among Saudi Arabia's most influential figures since being named second-in-line to the throne last year.
His visit to Washington come after Central Intelligence Agency chief John Brennan said on Saturday that secret findings of a 2002 congressional investigation into the 9/11 terror attacks should not be taken as evidence of official Saudi complicity.
A decision is expected soon on whether to release a classified 28-page section of the report by the House and Senate intelligence committees.
Riyadh insists it has nothing to fear from release of the pages.
Fifteen of the 19 Al-Qaeda plane hijackers were Saudi nationals. Their attacks on September 11, 2001 killed nearly 3,000 people.
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