Perez’ earliest big-time gig was co-hosting the noontime variety programs Family Kuarta o Kahon (1986–1990), Eat Bulaga! (1989–1995), Sa Linggo nAPO Sila (1990–1995), ‘Sang Linggo nAPO Sila (1995–1998), and Magandang Tanghali Bayan from 1998 until she left in 2002. After two years to quit hosting variety shows, she was chosen to be one of the hosts for the morning talk-variety show M.R.S..

As an actress, Amy Perez played a variety of roles in television and movies. She took the role of Anne in Anak ni Baby Ama and also appeared in Flavor of the Month, starring Joey Marquez and Alma Moreno. It was in these movies that she was discovered to have much flair for comedy. Perez’ performance as Helen in the Robin Padilla-starrer Sa Diyos Lang Ako Susuko is one of the roles for which she received critical acclaim. She also starred in Petrang Kabayo 2: Ang Ganda-Ganda Ko, Palibhasa Lalake, Ipagpatawad Mo, Tigasin and Pera o Bayong (Not da TV). She appeared in television dramas like Sa Dulo Ng Walang Hanggan in which she played the role of Mirriam, Habang Kapiling Ka as Divine Ogata and Ikaw Sa Puso Ko in 2004. Moreover, she appeared in the two episodes of Komiks in 2006: 1. Alpha Omega Girl; 2. Agua Bendita. There was also a segment entitled Kama in a horror flick directed by Jose Javier Reyes Matakot Ka sa Karma in which she took the role of Myrna. She was also a star in an episode of Love Spell, “Shoes ko po, Shoes ko Day!” just last 2007 and she was a character in I’ve Fallen for You, which she played Ninang Beth.

Perez and musician Brix Ferraris have a son named Adi. She is a cousin of veteran actress Lorna Tolentino. She filed for annulment from Ferraris but was denied by the Supreme Court. Perez then met her current partner, radio host Carlo Castillo (younger brother of GMA News reporter and anchor, Cedric Castillo). They have a son together born in 2008. In 2012, Perez was confirmed to be 3 months pregnant, her second child to Castillo, and she confirmed that she was to take a 1-year leave from Face to Face.