Later that day he will travel to Frankfurt to meet with European Central Bank President Mario Draghi.
On April 9, Lew will meet with German Finance Minister Wolfgang Schaeuble in Berlin. In the afternoon, he will travel to Paris to meet with French Finance Minister Pierre Moscovici before heading back to Washington that evening.
Lew's trip comes about two months ahead of the expected start of trade talks between the United States and the European Union, which could take upward of two years to complete.
The 27-nation EU and U.S. trade officials argue that the trade deal is now needed to boost the economies on both sides of the Atlantic.
Lew also is likely to address the near-collapse of the Cyprus economy, which is adding weight to an already stressed financial environment in Europe.
The tiny island nation was facing bankruptcy before a multi-billion dollar bailout plan crafted by the EU and the International Monetary Foundation helped contain the crisis.
The bailout puts severe restrictions on how many euros people can take out of the country until the situation is more settled.
Banks reopened Thursday for the first time in nearly two weeks and, on Friday, Cyprus President Nicos Anastasiades said the nation won't leave the euro.