Del Castillo was born in Mexico City, Mexico. She is the daughter of Kate Trillo and Eric del Castillo, a legend of Mexican cinema and a soap opera actor himself. Del Castillo has two siblings: a sister, the journalist Verónica del Castillo, and a half-brother, Ponciano, from her father's side.
She made her acting debut in 1978 when she took part in a film called The Last Escape. She became well known in 1991 when she starred as Leticia in Muchachitas, a telenovela airing in several Latin American countries, as well as in La Reina del Sur and series Dueños del Paraíso for the Telemundo network and in other telenovelas as a leading actress.
In 2002 and 2003, she embarked on an international tour alongside Argentine actor Saul Lisazo with the play Cartas de Amor (Love Letters). In November 2007, she was named one of the "Stars of the Year" and in 2011 one of the "25 most influential women" and "50 most beautiful" by People en Español magazine. In 2006, Del Castillo starred in the film Bordertown, which became her first role in Hollywood. In 2009, del Castillo was appointed Ambassador for the Mexican Commission on Human Rights and the following year she helped launch the Blue Heart Campaign in order to raise awareness and fight human trafficking. She starred in the film Colosio: El asesinato, which centers around the assassination of the Mexican presidential candidate Luis Donaldo Colosio.
She has appeared in advertising campaigns for companies such as L'Oréal and Ford, and in the music video "Fuego de Noche, Nieve de Día" by Ricky Martin.
In November 20, 2015 she launched in association with the Vivanco Family a new brand of tequila named Tequila Honor del Castillo. She is the spokesperson representing the brand.
One of her first known romantic relations was with Emilio Azcarraga Jean son of media mogul Emilio Azcárraga Milmo, and now CEO of the largest mass media company in Latin America, the Televisa Grup.
On February 3, 2001, she married football player Luis García. The marriage was dissolved on September 1, 2004. Del Castillo lives in Los Angeles. On August 22, 2005, it was reported by the LAPD that del Castillo's new house in Los Angeles had been broken into by thieves, who took some jewelry from the actress. Del Castillo was in Los Angeles filming Bordertown, a film about the female homicides in Ciudad Juárez, when the robbery occurred. In August 2009, del Castillo married Aarón Díaz in a Las Vegas ceremony. On July 26, 2011, it was announced that Kate and Díaz were separating.
In 2012, she posed in a PETA ad campaign encouraging pet owners to "fiercely protect" their dogs and cats by keeping them indoors.
During an interview with Cristina Saralegui on the Cristina Show, Kate revealed that her favorite band is the English new wave band Duran Duran.
She became a citizen of the United States in September 2015 and currently lives in Los Angeles.
On January 9, 2012, del Castillo publicly posted an essay talking about social issues in Mexico that included a controversial request to Joaquín Guzmán Loera, the then at-large head of the Sinaloa Cartel, on her Twextra page (which is associated with Twitter), stating:
"The government has numbed us, we are manipulated, and I say Mr. El Chapo lets go traffic with unknown well-being, lets do good to the world, you know how to trade, deal with love, with good things'. "Life is a business and the only thing that changes is the merchandise. Don’t you agree?", “Mr Chapo, wouldn’t it be cool that you started trafficking with love?” "Today I believe more in Chapo Guzmán [than in] the government that hides painful truths from me, who hide the cure for cancer, AIDS, etc., for their own benefit and wealth."
Del Castillo was contacted by Guzman's lawyer to talk about producing a biographical film about Guzman in 2014. As a result, she was placed under CISEN surveillance. Communication increased following Guzman's escape from prison in July 2015. She brokered an interview between American actor Sean Penn and Guzmán in October 2015, shortly before Mexican Marines recaptured him. She received a cell phone and the codenames Hermosa and Dama from Guzman. Penn and del Castillo recommend the American lawyer Joshua L. Drakel. CISEN released photographs of del Castillo at the meetings with Guzman's lawyer and of the arrival of the actress and Sean Penn to Mexico.
Authorities found DVDs of La Reina del Sur at the safe house stormed during Guzman's capture.
Sean Penn and Del Castillo's actions are under investigation by the PGR. She was subpoenaed on January 18 and will testify before the public prosecutor at the Mexican Consulate in Los Angeles. She is under investigation as to whether Del Castillo received illicit money to finance the planned movie about Guzman and her tequila brand Honor del Castillo.
On February 5, 2016, a Mexican judge granted del Castillo's petition for an injunction against any arrest related to the federal investigation into her ties with Joaquín Guzmán. The Mexican Attorney General issued a detain-and-interrogate order on del Castillo; however, that would only become effective if del Castillo sets foot on Mexican soil. That order was issued after she did not heed a request to voluntarily appear before Mexican prosecutors.