Governor R.S. Mooshahary administered the oath of office to the 47-year-old leader who was seen as the architect of the Congress's victory in the assembly elections in this mountainous northeastern state, on the lawns of the Raj Bhavan.
Mukul Sangma will announce the list of his council of ministers later this week.
"I have been directed by madam (Congress chief Sonia Gandhi) to take oath alone and will expand the ministry after consultation with party high command," Mukul Sangma told IANS.
The Congress emerged the single largest party with 29 seats - two short of a majority in the 60-member house. The Nationalist Congress Party (NCP), which secured two seats, and 11 independent legislators have extended "unconditional support" to the Congress.
Party sources said Sonia Gandhi endorsed Sangma's name as the Congress Legislature Party (CLP) leader for the impressive wins in the Garo Hills region, considered the stronghold of her bete noire, former Lok Sabha speaker Purno A. Sangma.
The Congress has won 13 of the 24 seats in Garo Hills districts, while the tribal-centric National People's Party (NPP) founded by Purno Sangma managed only two.
James Sangma, the eldest son of Purno Sangma, and Nihim D. Shira were the only NPP candidates who managed to win.
In 2008, the Congress won seven seats in the Garo Hills, while the NCP, under Purno Sangma's leadership, won 15 seats in the state, including 13 in the Garo Hills.
Mukul Sangma took oath as the state's 26th chief minister in the presence of hundreds of Congress legislators, leaders of other political groupings and senior government officials.
He first assumed office April 20, 2010, replacing veteran Congress leader D.D. Lapang.
Mukul Sangma, a medical practitioner, gave up his government job as medical and health officer in Tura health centre and plunged into the electoral fray in 1993.
He contested and won the Ampatigiri assembly constituency in West Garo Hills as an independent candidate. There was no looking back for him since then.
At the age of 33, Mukul Sangma bagged a cabinet berth and held various posts as minister of taxation, information and public relations and others.
In 2005, he was appointed deputy chief minister in-charge of home and education departments. But he was forced to quit after the Garo Hills police firing, in which nine people lost their lives, over the Meghalaya Board of School Education issue.