In 1999, she was chosen to play her first big role, Luisana Maza in Chiquititas at the age of 12, a popular television series created by Cris Morena.

[citation needed] Lopilato signed a contract with the Cris Morena Group, and released four Chiquititas soundtrack albums — Chiqutitias Vol.

She was nominated for an ACE Award for Best Supporting Actress for her role onstage in Arlequín, and appeared in the Martín Fierro Award-nominated television comedy El Capo.

[14] In June 2009, FHM magazine in Spain, ranked her 86 in its annual Las 100 mujeres más sexys del mundo.

[15] In 2010, Lopilato completed the Channel 13 TV series Alguien que me quiera, in which she played Bianca Rivera, a sweet and sensitive young woman who struggled and suffered much for love.

In November 2010, FHM in Spain ranked her 17th on its annual list Las 100 mujeres más sexys del mundo.

[citation needed] In 2011, Lopilato made her first film outside Argentina, the Spanish thriller Predeterminados (directed by Jordi Arencón), as "Vera".

[17] Lopilato joined the cast of the El Trece series Lobo as a villainess, opposite Ana Linares's character (Vanesa González).

In 2013, she played a young cancer victim in the second season of the Argentine remake of In Treatment, En terapia, starring Diego Peretti and broadcast by TV Publica.

After the premiere in September, she announced her next film project, Los que aman, odian, based on the book by Adolfo Bioy Casares and Silvina Ocampo.

She went to Hollywood acting in her first North American film entitled Fair Market Value; the cast included Tina Benko and Wendy Makkena.

Two years later, as the group dissolved, the series was sold to Spain and the success of its music lead to a fourth and fifth album, this time a compilation entitled, El Disco de Rebelde Way (2006) and Erreway en Concierto (2006), and a show in Israel in 2004.

She has worked for[clarification needed] such brands as 47 Street, Nazaria Zapatos, Prosegur, Keff, John Foos, Ultimo, Axe, Motor Oil Underwear for Juniors, BlackBerry, Kukuloco, Rebelde Way underwear, Sugus Combinados, Pent Ten, Swatch, Marcela Koury, Ona Saez Jeans, Ripley S.A., Promesse, Bubbaloo, Despegar, Coca-Cola, McDonald's, Gottex, Vitamina, L'Oréal Elvive, Gillette and Alberto VO5.

Lopilato became engaged[20] to Canadian singer Michael Bublé in 2009, having appeared in his music video for "Haven't Met You Yet"[21] which was written for her.