Locsin was born on April 23, 1985 in Santa Maria, Bulacan. Since the age of 14, she has lived with her father, Angelo Colmenares, and has had no contact with her mother. She studied at St James College in Quezon City for her primary education and finished high school at the University of Santo Tomas High School in Manila. In August 2007, she attended a short-course for fashion design at Central Saint Martins College of Art and Design in London. Despite being of Christian faith, she is a part of a Muslim Royal Family in Marawi City in the province of Lanao del Sur through her mother.
Locsin was discovered at a shopping center by a talent scout. She then auditioned for several commercials and was supposed to be a part of ABS-CBN's Star Circle Batch 9, but failed to sign a contract because her father opposed the idea. Later, she became a contract star of GMA Artist Center, first appearing on the second season of the teen-oriented series, Click and was also included in the cast of Ang Iibigin Ay Ikaw.
In August 2004, Locsin starred in the fantasy-themed TV series Mulawin, alongside Richard Gutierrez, wherein she portrayed, "Alwina", one of the two main protagonists. The show was a huge success and received high ratings until its finale on March 2005.
Following the success of Mulawin, Locsin was cast in the title role as Darna in the 2005 fantasy-themed TV series of the same name. The show was also highly regarded by the public, gaining immensely high ratings and surpassing the records set by her previous TV show. Darna's pilot week average is 50.08% and its highest rating was 52.1% while the lowest was 33.3%.
Locsin starred in another fantasy-themed TV series, Majika, together with Dennis Trillo, which was aired from March to September 2006. She played the role of Sabina, a seemingly ordinary girl who lived in the world of mortals but is unknowingly the one destined to become the most powerful female magician. Afterwards, she was cast in Asian Treasures, opposite Robin Padilla. It was the first Philippine TV series that was shot in multiple countries such as Mongolia, Thailand and China. The show was aired from January to June 2007. Both shows were also well received.
In August 2007, Locsin signed a two-year exclusive contract with ABS-CBN. Her first acting appearance with the network was via Maalaala Mo Kaya in the episode "Pilat". Her performance gained her the Star Award for TV for Best Single Performance by an Actress. By January 2008, she launched her first drama series with the network entitled Lobo, together with Piolo Pascual in the lead role. She earned an International Emmy Award for Best Performance by an Actress nomination for her performance in the series. She also received an Ani ng Dangal Award for her iEmmy nomination and another Ani ng Dangal Award for Lobo's international recognition in BANFF Canada. In 2009, Locsin starred in the top-rated TV series, Only You, a Philippine remake of the Korean drama of the same title aired by SBS Korea in 2005. She starred alongside Sam Milby and Diether Ocampo. The show was directed by Rory Quintos and was the 3rd Most Watched TV Series of 2009 based on TNS survey.
Later in 2010, she starred in the TV series Imortal, the sequel to her earlier work, Lobo, together with John Lloyd Cruz. It was directed by Chito Roño. The shows website had 15 million hits in just 3 months. It had a game entitled "Pangil" and webisodes downloaded in a weekly basis. It won an Anvil and Quill Award.
In 2011, she became a guest star in the comedy sitcom, Toda Max. However, her guesting eventually turned into a regular stint.
In 2014, Locsin returns to primetime TV after three years through the hit series, The Legal Wife, together with Jericho Rosales, Maja Salvador and JC de Vera. The series was directed by Dado C. Lumibao and Rory Quintos. Due to high ratings, the show helped in dropping the crime rate as reported by PNP.
Locsin also became a Pilipinas Got Talent judge. She happened to have two Maalaala Mo Kaya two- part episodes, one SAF tribute and one Mother's Day Special. In 2017, she guested in La Luna Sangre as Lia.
Locsin's first film appearance was in 2000 via Ping Lacson Supercop, wherein she played the role of a young Robina Gokongwei. She later on made a cameo appearance in Mano Po 2 in 2003 and starred in the teen-oriented movie Kuya in 2004 as well as in the comedy film Singles. Also, she starred in the drama film Mano Po III: My Love and in the horror film Sigaw which were both entries to the 2004 Metro Manila Film Festival.
In 2005, Locsin with Richard Gutierrez starred in the romantic film Let the Love Begin, released under GMA Films. She and Gutierrez also reprised their roles as Alwina and Aguiluz in the movie adaptation of the TV series Mulawin, which was an entry to the 2005 Metro Manila Film Festival.
Early in 2006, Locsin starred in the romantic movie I Will Always Love You. She also starred in the horror film TxT and in the romantic drama-comedy film Mano Po 5. The latter was an entry to the 2006 Metro Manila Film Festival.
Locsin reunited with Gutierrez in the romantic drama film The Promise in 2007 where their roles were considered more mature than the previous films they both starred in. She had also produced her own film entitled Angels, which was shown in theaters on April 2007.
In 2009, she starred in the movie Love Me Again together with Piolo Pascual in the lead titles and made a cameo in the romantic comedy film, My Amnesia Girl in 2010.
Locsin gained critical acclaim in her 2011 drama film with Aga Muhlach, In the Name of Love. Her performance garnered her several accolades including the Star Award for Movies for Movie Actress of the Year, the Gawad PASADO Award for Pinakapasadong Aktres, and a nomination for best actress at the FAMAS Awards.
She reunited with John Lloyd Cruz in the romantic comedy film Unofficially Yours in 2012 and then starred, together with Dingdong Dantes and Angelica Panganiban in the drama film One More Try, Star Cinema's entry to the 2012 Metro Manila Film Festival. Locsin's performance in the latter was highly praised by film critics and media personalities and earned her the Star Award for Movies for Movie Actress of the Year for the second year in a row, the FAMAS Award for Best Actress and the Film Academy of the Philippines Award for Best Actress.
In 2016, she was awarded by both mainstream and indie film enthusiasts as she received #LifePeg or Lifetime Achievement Award from Star Cinema and Aktres ng Dekada Award from Inding- Indie Awards. She also starred opposite Vilma Santos in Everything About Her and won Best Supporting Actress in the 1st Eddy Editor's Choice Awards. She also had an LGBT- themed movie The Third Party in which she play the title role. She is set to star in a Star Cinema movie entitled "Wife, Husband, Wife" and this will be her reunion movie with Richard Gutierrez and Angelica Panganiban.
On April 23, 2007, Locsin celebrated her birthday with GABRIELA Foundation, an NGO that supports women and children. On April 20, 2008, Locsin organized a gift-giving to the less fortunate children in Payatas, Quezon City and gave poor children food, clothing and other basic needs. It was her birthday gift supported by her sponsors.