Her adoptive family claimed she was found on September 3, 1968, in Iloilo City by a woman, in the holy water font of Jaro Metropolitan Cathedral, the main church of the city. When the infant was discovered, the parish priest named her "Grace" in the belief that her finding was through the grace of God; she was christened by Jaime Sin, the Archbishop of Jaro, who would later become Archbishop of Manila. Although the cathedral issued an announcement in the hopes that her biological mother would claim her, no one stepped forward. Grace was taken in by the Militar family, with Sayong Militar's in-law Edgardo, who was a signatory on the child's foundling certificate, considered to be her possible father. Sayong Militar later passed Grace on to her friend Tessie Ledesma Valencia, an unmarried, childless heiress of a sugar baron from Bacolod, Negros Occidental.

In 1975, she attended elementary school at Saint Paul College of Pasig and Saint Paul College of Makati. In 1982, Poe transferred to Assumption College San Lorenzo for high school. Following high school, Poe entered the University of the Philippines Manila (UP), where she majored in development studies. She transferred to Boston College, where she graduated with a degree in political science in 1991. She interned for william Weld's campaign while in college.

Poe married Teodoro Misael Daniel "Neil" Vera Llamanzares on July 27, 1991. Llamanzares is a natural-born Filipino who held American citizenship since birth until April 2016. He is a veteran of the United States Air Force who served from 1988 to 1991 and later worked for Science Applications International Corporation. He worked for San Miguel Corporation after the return of his wife to the Philippines.

On April 16, 1992, Poe gave birth to her son, Brian, a Journalist who worked as a reporter for CNN Philippines. She later gave birth to two daughters: Hanna in 1998, and Nikka in 2004. Her family lived in Fairfax, Virginia, for 12 years.

Poe worked as a preschool Teacher at a local Montessori education-style school in 1995. In 1998, she left her job as a Teacher to work as a procurement liaison officer at the United States Geological Survey. In 2005, she was made Vice President and Treasurer of her father's film production company, FPJ Productions, and was put in charge of maintaining the company's archive of over 200 films.

The MTRCB under Poe's tenure also implemented policies and programs to promote "intelligent viewing", such as promulgating the implementing rules and regulations for the Children's Television Act of 1997 some fifteen years after its passage, and enforcing restrictions on the type of viewing material that can be shown on public buses. Despite this thrust, Poe has spoken out against restrictions on freedom of expression, preferring self-regulation to censorship. During this time, she encouraged the creation of new cinematic output through the reduction of review fees despite cuts to its budget, and has promoted the welfare of child and female actors.

Poe is a natural-born Filipino. On October 18, 2001, Poe acquired U.S. citizenship by naturalization. She reacquired her Philippine citizenship and in October 2010, she renounced her American citizenship, as per the RA 9225 law.

In 2003, her adoptive father, Fernando Poe, Jr. announced that he was entering politics, running for President of the Philippines in the upcoming election under the Koalisyon ng Nagkakaisang Pilipino (KNP) against then-President Gloria Macapagal-Arroyo. Poe returned to the Philippines to help him campaign, but returned to the United States afterward.

While Poe herself admitted that her biggest strength in the campaign was her surname, she also conceded that it would be insufficient for her to be elected simply on that alone, emphasizing that her platform is just as important as her name in getting her elected to the Senate. She also dismissed claims that her candidacy was her family's revenge against her father's loss in 2004, saying that all she wants to do is serve should she be elected to the Senate. A day after the election, Poe was announced as among the winners with her having the highest number of votes. She was officially proclaimed a senator by the COMELEC board on May 2013, along with fellow Team PNoy candidates Chiz Escudero, Sonny Angara, Alan Peter Cayetano, and Loren Legarda, as well United Nationalist Alliance candidate Nancy Binay (who did not attend, opting instead to send her Lawyer to represent her).

Poe studied at the University of the Philippines Manila, where she majored in development studies, but moved to Boston College in Massachusetts, United States where she finished a degree in political science and has spent much of her adult life in Fairfax, Virginia. In 2004, her adoptive father ran for the Philippine presidency against the incumbent, Gloria Macapagal-Arroyo, but was defeated; he died months later. On April 8, 2005, Grace returned to the Philippines after learning that her father had died. She began pursuing her father's rights over the results of the election and campaigned against alleged electoral fraud.

In the 2010 general election, Poe served as a convenor of Kontra Daya. She also became honorary chairperson of the FPJ for President Movement (FPJPM), the group which was organized to pressure her father to run in 2004, continuing the movement's social relief programs for the less fortunate. On October 10, 2010, President Benigno Aquino III appointed Poe to serve as chairwoman of the Movie and Television Review and Classification Board (MTRCB). She was sworn in on October 21, 2010, at the Malacañang Palace and was later reappointed by President Aquino for another term on October 23, 2011.

Analysts noted the rapid rise of Poe in national election surveys, which community organizer Harvey Keh attributed to popular sympathy for her father, fueled in part by high public trust in the Poe name. Prior to the start of the election season, Poe was ranked twenty-eighth in a preliminary survey conducted by the Social Weather Stations (SWS) in mid-2012, before the start of the filing period. Immediately after filing her candidacy, Poe initially ranked fifteenth in the first survey of the election, published by StratPOLLS. While she ranked as low as twentieth in a survey published by SWS later in the year, she entered the top 12 in January 2013, where she stayed. In the last survey issued by Pulse Asia in April 2013, she was ranked third.

In the 2013 elections, Poe ran on an eleven-point platform promising to continue the legacy of her father. Her labor legislative agenda also includes more opportunities, skill development and growth for Filipino workers, employment security for the disabled and handicapped, and protection of workers in the informal sector. Specific policies she advocated in the course of her campaign include reviving the national elementary school lunch program first introduced during Marcos Era, the installation of closed-circuit television cameras in government offices, and stricter penalties against child pornography, continuing her earlier advocacy during her time at the MTRCB. In addition, she has also advocated against Internet censorship.

While at the MTRCB, Poe had advocated for a "progressive" agency which would have enabled the television and film industries to help the Philippine economy, with her tenure being marked by an emphasis on diplomacy. At the beginning of her term, Poe instigated the implementation of a new ratings system for television programs, which she said was "designed to empower parents to exercise caution and vigilance with the viewing habits of their children". This was complemented by the implementation of a new ratings system for movies—a system which closely follows the new television ratings system—at the end of her term.

On November 17, 2015, the Senate Electoral Tribunal opted to drop the cases against her. The decision was affirmed on December 3, 2015. In their judgment on the case, the SET declared that Grace Poe, a foundling, is a "natural-born Filipino", which allowed her to retain her seat in the Philippine Senate. David filed a motion for reconsideration to reverse the ruling by SET, which was rejected on December 3, 2015, after which he filed an appeal with the Supreme Court. On December 1, 2015, the COMELEC's second division disqualified her as presidential candidate due to failing to meet the "10-year requirement" for residency. Under COMELEC rules, the party or coalition supporting her may file a substitute before December 10, 2015. On December 11, the commission's first division also disqualified Poe. The first division, voted 2–1 in favor of the petitions to disqualify and cancel her certificate of candidacy. These decisions were appealed to the COMELEC en banc, which on December 23, 2015, formally disqualified Poe from running as President in the 2016 elections for failing to meet the 10-year residency requirement. Poe said she would appeal the disqualification to the Supreme Court. On December 28, 2015, the Supreme Court issued two temporary restraining orders against the decision of the COMELEC en banc.

Poe is in favor of the passage of the Anti-Discrimination Bill (now SOGIE Equality Bill). The LGBT sector was one of the sectors she prioritized and thanked during her 2016 presidential bid. She was not in favor of same-sex marriage during a 2013 interview and instead was in favor of domestic partnership, however, she changed her mind and announced her all-out support for same-sex marriage in 2016, the first and only presidential candidate in Philippine history to do so.