Agoncillo was born on April 10, 1979. Growing up in an upper-middle-class family, he attended private schools from elementary to college. He finished elementary and high school at San Beda College Alabang.
He graduated from De La Salle University-Manila with a Bachelor of Arts degree in organizational communication.
Agoncillo started as a model at the age of fifteen, beginning as one of the early Penshoppe's Club Pen models. He has appeared in various television commercials for a variety of products such as Greenwich Pizza (together with Donita Rose), Sprite, Smart Telecommunication, Emperador Brandy and Swish mouthwash.
Agoncillo became one of the original hosts of Mornings @ GMA, an early morning variety program of GMA Network. He also hosted Campus Video, a short-lived program shown every Saturday mornings at GMA Network.
He moved to ABS-CBN, and became a co-host in Talk TV, a late morning talk show co-hosted by broadcasters Julius Babao and Christine Bersola-Babao, and actress Janette McBride. Agoncillo was briefly paired with co-host Janet McBride. Rumors spread that the two were exclusively dating for a period of time.
He also hosted Breakfast, an early morning variety program; Star in a Million, with Edu Manzano and Zsa Zsa Padilla, and Y Speak, a youth-oriented talk show and debate forum. Both shows are still aired in Studio 23, an ABS-CBN subsidiary. He won his first KBP Golden Dove Awards for his Best Talk Show host in 2005 for Studio 23's Y Speak.
Agoncillo was the main host of Philippine Idol alongside fellow ABS-CBN actress Heart Evangelista on ABC-5 (now TV5) before it was moved to GMA Network and rebooted into Pinoy Idol.
In August 2008, he began hosting TV5's Talentadong Pinoy, which showcases Filipino undiscovered talents. He also hosted Endemol's Pinoy Fear Factor which aired on ABS-CBN. Pinoy Fear Factor was shot entirely in Argentina.
On October 24, 2009, Agoncillo joined Eat Bulaga! replacing long-time host, rapper Francis Magalona, who died a week prior.
From April 2010 to February 2011, Agoncillo co-hosted the noontime musical variety show P.O.5 on TV5.
For his hosting stints in Eat Bulaga! and Talentadong Pinoy, Agoncillo became a four-time awardee of the Aliw Award for Best Male Emcee, for which he won consecutively from 2007 to 2010. In 2010, he was elevated to the Hall of Fame.
Agoncillo hosted a game show called Picture! Picture! which premiered on November 23, 2013 on GMA Network, the show aired for 28 weeks ending on June 15, 2014.
In 2015, Agoncillo was announced as the host of Cash Cab Philippines, the Philippine edition of the game show format Cash Cab. The show will air 13 episodes on AXN Asia from December 22.
Agoncillo joined the talent cast of ABS-CBN. He is most memorable for playing the love interest of Judy Ann Santos in the television soap opera Krystala. He again appeared with Santos in the movie Kasal, Kasali, Kasalo. He received best actor nominations from different award-giving bodies for his portrayal of a confused newly wed husband in this film. He will be doing a new movie with Judy Ann Santos called Mr. Housewife.
He also played a main cast role in Bituing Walang Ningning, an ABS-CBN soap opera featuring singer-actresses Sarah Geronimo, Angelika dela Cruz, and Zsa Zsa Padilla in the leads.
Agoncillo also played leading roles in independent film projects and television drama shows. He played the distinct roles of a grease-filled beggar and a transvestite in two separate dramatic episodes of Maalaala Mo Kaya, the biographical drama series of ABS-CBN.
He starred in the ABS-CBN television series, Ysabella with his long-time on-screen partner, Judy Ann Santos.
Agoncillo returns to acting on TV with drama series entitled Pieta airing weekday afternoons over ABS-CBN wherein he portrayed Rigor, a character originally portrayed by Ace Vergel.
Agoncillo returns to acting again for his new role in May Bukas Pa (in a final episode) where he plays a media cameraman after his wife Judy Ann Santos also guested in the show (in a different episodes).
Agoncillo appeared in Lady Dada on TV5 in 2010.
Agoncillo returned to acting again for his very first television role on GMA in My Husband's Lover (also in a last week of the drama series), with his co-stars Carla Abellana and Dennis Trillo in 2013.
Ryan announced his engagement to actress Judy Ann Santos. They confirmed their engagement on June 19, 2008.
After months of speculation, Ryan Agoncillo and Judy Ann Santos got married in a private wedding on the early morning of April 28, 2009, at the San Juan de Nepomuceno Church in San Juan, Batangas, Philippines.
Agoncillo and his wife are now parents to daughter Johanna Louis (Yohan) and son Juan Luis (Lucho). In June 2015, Santos and Agoncillo both announced that they are currently expecting a third child. A daughter named Juana Luisa (Luna) was born in 2016.
Agoncillo had a one-man colored photo exhibit at Glorietta sponsored by Fujifilm in 2007. He published a black-and-white photography coffeetable book titled "Ploning - the Making" as a birthday gift to his fiancee, Judy Ann Santos in 2008.
Agoncillo is a motorcycle enthusiast. He is also into drifting. He competes in drifting events with a Nissan Silvia (S13) sponsored by Adidas, Yellow Cab Pizza, Shell and Nexen Tire.I'll Have to Say I Love You in a Song
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Nominated, Best Actor, 2011 PMPC Star Awards for Movies
Anak TV " Awards 2010 - Favorite Anak TV Makabata Star
"Hall of Fame" Aliw Awards 2010 - Best Male Emcee
"Anak TV Seal Award" - 2010 with wife Judy Ann Santos
Winner, Best Talent Show Host - 2009 PMPC Star Awards for TV
Winner, Male Star Of The Night - 2009 MTRCB TV Awards
Winner, German Moreno Youth Achievement Award 2008 - FAMAS Awards Night 2008
Winner, Best Public Affairs Program Host "Y-Speak" - 2007 KBP Golden Dove Awards
Winner, Best Emcee - 2007, 2008 & 2009 Aliw Awards
Winner, Most Admired Male TV Personality - 2009 Anak TV Seal Awards
Nominated, Best Actor for "Kasal...Kasali...Kasalo, FAMAS Awards 2006
Nominated, Best Supporting Actor for "Kutob", FAP Awards 2006
Nominated, Best Actor (Pinakamahusay na Pangunahing Aktor), Gawad Urian Award 2007
Outstanding Original Reality Competition Program Host, 8th ENPRESS Golden Screen Awards 2011