Former central bank governor Darmin Nasution was named to the important post of chief economics minister, while prominent private equity executive Thomas Lembong was appointed the new trade minister.
Four other ministers were replaced in the reshuffle, which followed months of speculation that Widodo planned changes after a poor start to his presidency.
Analysts broadly welcomed the news, particularly the decision to appoint Nasution who is seen as a safe pair of hands and a reformer.
Wellian Wiranto, an economist with Singapore-based OCBC Bank, said there was hope that Nasution will "have a better chance at coordinating economic policies among the myriad of ministries and agencies which have been largely lacking thus far".
Presidential spokesman Teten Masduki said the changes had been made to create a "stronger, consolidated government".
Widodo was inaugurated in October after winning power on a pledge to boost Southeast Asia's biggest economy, which has been slowing in recent years as demand for its key commodities exports decline.
His administration has notably failed to kickstart a promised flurry of major infrastructure projects, seen as crucial to attracting foreign investment and raising growth. Many ministries face criticism for only spending a fraction of their budgets.
Widodo got off to a promising start by cutting huge fuel subsidies that were seen as a drag on growth but since then his performance has generally disappointed investors.
While the focus of his reshuffle was economic, Widodo has also suffered falling popularity as disappointment grows at his failure to tackle vested interests and corruption in one of the world's most graft-ridden countries.
His failure to defend the popular anti-graft agency from attacks by the notoriously corrupt police, during a row over the appointment of a controversial new police chief, severely dented his credentials as a corruption fighter.
