When Archbishop Mariano Gaviola of Lipa retired, Rosales was appointed his successor on December 30, 1992, bringing the latter back to the diocese where he began his ministry.

With the announced retirement of Cardinal Jaime Sin, Rosales was named archbishop of Manila by Pope John Paul II on September 15, 2003.

Archbishop Antonio Franco, the Apostolic Nuncio, personally made the announcement at Manila Cathedral during a Mass for the 40th anniversary of the Focolare Movement.

A little later, Benedict added, "I am counting on you, dear Brother Cardinals, to ensure that the principle of love will spread far and wide, and will give new life to the Church at every level of her hierarchy, in every group of the faithful, in every religious institute, in every spiritual, apostolic or humanitarian initiative.

"[citation needed] On February 3, 2007, Rosales was appointed for a five-year term on the 15-member Council of Cardinals for the Study of Organizational and Economic Concerns of the Apostolic See.

[5] Four months after his 79th birthday, Rosales resigned as Archbishop of Manila and he was succeeded by the then-Bishop of Imus, Luis Antonio Tagle upon the latter's installation on December 12, 2011.

When the state of national emergency was proclaimed, he would ask Filipinos to pray for peace and unity in the country and expressed hopes that the government will not abuse and curtail the rights of the people.

In 2007, Cardinal Rosales argued against the National Statistics Office (NSO) requirement that all solemnizing officers/priests undergo training before conducting wedding ceremonies.

"[7] In 2008, Rosales clashed with Ang Ladlad founder Danton Remoto on the subject of allowing gays to participate, in drag, in the Flores de Mayo celebration.

[9] The guidelines that Rosales wrote for implementing the 2007 motu proprio Summorum Pontificum were reported to have been criticized by Darío Castrillón Hoyos, President of the Ecclesia Dei Commission, as too restrictive.