Melamede was born in New York City, while her mother, Israel Prize-winning architect Ada Karmi-Melamede, was a lecturer in the Department of Architecture at Columbia University. Her maternal uncle, the architect Ram Karmi, and her grandfather, the architect Dov Karmi. Following her sister and brother's enlistment in the army, her parents returned to Israel. Melamede decided to stay in the United States and enrolled in architecture studies at Yale University. In 1997, after working with her mother for a year and a half, she decided to abandon architecture and pursue filmmaking. She returned to New York City and studied film in an intensive six-week course at New York University. She began working as an intern, then as an assistant. In 2003, Melamede and Eva Kolodner founded the production company Salty Features; a few years later, her partner, Kolodner, left the company. The most expensive film she has produced is "Brief Interviews with Disgusting People," written and directed by John Krasinski (who plays Jim, the star of the series "The Office" with a budget of nearly five million dollars. It is an adaptation of the short story collection by David Foster Wallace. The film My Architect, which Melamede produced and directed by Nathaniel Kahn, was nominated for an Oscar in 2004. The film "Inocente" is directed by Sean and Andrea Payne. The protagonist of the film "Inocente" is fifteen-year-old Inocente, the daughter of illegal immigrants from Mexico. She was abused by her father and mother and has moved between thirty housing places for the past nine years, including: an abandoned warehouse, a homeless shelter, a public park and a friend's house. Despite the conditions in which she grew up, Inocente becomes a talented painter who sells her paintings at exhibitions, rents a one-room apartment, and for the first time in her life, she lives in her own apartment. Before the film was completed, the production budget ran out. To solve this, Melamed and her colleagues went on a public fundraising spree. She used the crowdfunding site "Kickstarter" and raised $52,000 from about 300 private donors. The film was screened at many film festivals and aired on MTV, which was one of its sponsors, during the initial fundraising phase. Melamed built a system of workshops around the film, in which students watch the film and, after the screening, are asked to draw a picture inspired by it. In 2024, her film "Ada - My Architect Mother" was released Yael Melamede is married to a British computer scientist, and they have one son.