Maria Jimenez said her older brother has given way and let her run for mayor in his stead.
She said she made her decision based on "divine guidance," and is set to file her candidacy on Thursday, the last day for local candidates to file their bids.
Other candidates for Manila mayor include Sen. Alfredo Lim, Vice Mayor Danilo Lacuna, Arnold Atienza and Rep. Rodolfo Bacani.
Sen. Panfilo Lacson earlier said he will run for Manila mayor but later decided to seek re-election.