Mathai, a 1974-batch IFS officer, moved into his office in the Ministry of External Affairs in South Block at around 9.25 AM and assumed charge of the top post.
He said maintaining an era of constructive cooperation in the immediate neighbourhood will be one of his priority tasks as Foreign Secretary.
On Indo-Pak relations, 59-year-old Mathai, who will have a two-year fixed tenure, said the mandate for the Foreign Secretary is to pave the way for a substantive dialogue with Pakistan on all issues.
"We have to try and work to restore trust and confidence...This is the mandate which has been given to me. Foreign Secretary is as much an institution as an individual. So I will continue this effort," he told reporters after taking charge.
"Continuity will be my watch word," he said.
To a question whether composite dialogue is the "right way" between India and Pakistan, the Foreign Secretary said, "The mandate is substantive dialogue on all issues of common concern."
Mathai, who has served in Indian missions in Vienna, Colombo, Washington, Tehran and Brussels, said India should develop "strong and cooperative relationship" with all global players.
"We need to keep in mind the need for very, very strong relations with countries in Latin America, Central Asia, South East Asia and the Gulf region," he said.
Outgoing Foreign Secretary Rao has been appointed India's Ambassador to the United States.