First vice president Myint Swe, a military nominee and second vice president Henry Van Tio, an Upper House parliament nominee, took oaths alongside him.
During the previous president's tenure, the position was widely considered no more than a ceremonial role while Suu Kyi held the reins of power in presidential matters.
That makes it vital for her to have a reliable proxy in office, especially as she manages the delicate power-sharing arrangement with the military, which ruled the country for nearly half a century and remains enormously influential.
"I pledge to strive for the major objectives of the Union government: rule of law; an improvement in socioeconomic conditions; national reconciliation and peace; and constitutional reform, which lays the foundation for building a democratic federal union", said Win Myint in an inaugural speech that followed his swearing in.
Many have speculated what will happen to the NLD in the post-Daw Aung San Suu Kyi era.
But talk of amendments to Myanmar's 2008 constitution is likely to rise heckles among Myanmar's still-powerful generals.
Myanmar's civilian government has come under worldwide pressure for its handling of a crisis in northern Rakhine state, where security forces have been accused of ethnic cleansing and serious human rights violations that have caused about 700,000 Rohingya Muslims to flee to neighboring Bangladesh.
A violent military crackdown has forced some 700,000 Rohingya - a long-persecuted stateless minority - over the border into Bangladesh since August.
Win Myint is part of Suu Kyi's inner circle - the pair campaigned together during the 1988 democracy protests against the then-junta, a movement that was violently suppressed.
For many years a political prisoner under the military that then ruled Myanmar, Suu Kyi can not become president because the junta-drafted 2008 Constitution bars those with foreign family, which directly aimed to bar Suu Kyi from becoming head of state.