Fontana was born in Curitiba, Paraná, Brazil on the 4th of July. In 1996 she made it to the finals of the Elite Model Look when she was just 13 and in the following year she moved from Southern Brazil to Milan, Italy, to start her modelling career.
In 1999, at the age of 16, Isabeli Fontana appeared in the Victoria's Secret lingerie catalogue. This created a huge controversy as Victoria's Secret had earlier stated that its policy was not to sign models younger than 21 years old. However, the publicity generated by this proved beneficial to Fontana and she quickly rose to fame. Soon after the Victoria's Secret shoot, she was signed by Versace, Ralph Lauren and Valentino.
Since 1999 she has modelled for Sports Illustrated Swimsuit Issue, Marie Claire, ELLE, Vogue, Harper's Bazaar, Numéro, i-D, Arena and many others.
Isabeli Fontana has been the face of a variety of advertising campaigns including Armani Jeans, Chanel, Colcci, Disritmia, Emporio Armani, Enrique Martinez, Helena Rubinstein, Hugo Boss, Hussein Chalayan, Massimo Dutti, M. Officer, Nicole Farhi, Oscar de la Renta, Peter Hahn, Philips, Ralph Lauren, Revlon, Roberto Cavalli, Rosa Chá, Saks Fifth Avenue, Tommy Hilfiger, Triton, Valentino, Versace, Victoria's Secret, Vivara and others.
In 2008, Isabeli Fontana made her debut on the Forbes The World's 15 Top-Earning Models list at place 11, having earned $3 million.
Isabeli Fontana was married to model Álvaro Jacomossi but they divorced in 2004. Their son, Zion, was born in 2003. Fontana married actor and model Henri Castelli on December 10, 2005 and their son, Lucas, was born on October 23, 2006 in São Paulo. Fontana and Castelli are separated now.