While a student at the conservatory of Saint Petersburg, Netrebko worked as a floor cleaner and did odd jobs at St. Petersburg's Mariinsky Theatre (home of the Kirov Opera). Later, she auditioned for the Mariinsky Theatre, where conductor Valery Gergiev recognized her from her prior work in the theater. He subsequently became her vocal mentor. Under Gergiev's guidance, Netrebko made her operatic stage debut at the Mariinsky as Susanna in Le Nozze di Figaro. She went on to sing many prominent roles with the Kirov Opera, including Amina in La Sonnambula, Pamina in Die Zauberflöte, Rosina in Il Barbiere di Siviglia, and Lucia in Lucia di Lammermoor.

In March 2006, Netrebko applied to become an Austrian citizen, receiving her citizenship in late July. According to an interview in the Austrian weekly news, she will live in Vienna and Salzburg. This has led to some backlash in Russia. Netrebko cites the cumbersome and humiliating process of obtaining visas (as a Russian citizen) for her many performances abroad as the main reason for obtaining Austrian citizenship.

In March 2007, Netrebko announced that she would be an ambassador for SOS Children's Village in Austria, and be a sponsor for the Tomilino village in Russia.

Netrebko became engaged to Uruguayan baritone Erwin Schrott in late 2007. In February 2008, Netrebko announced that she and Schrott were expecting their first child later that autumn.

In 2003, Netrebko released her first studio album, Opera Arias, which became one of the best selling classical recordings of the year[citation needed]. The Russian Album was released in 2006, accompanied by the Mariinsky Theatre Orchestra, conducted by Valery Gergiev. The album reached the top ten in the German pop charts. In March 2007, she released Duets with Rolando Villazón. In 2007 she recorded a track with world famous violin player, Joshua Bell.

Time Magazine placed her on its Time 100 list in 2007. She was identified by the journal Musical America as “a genuine superstar for the 21st century” and was named 'Musician of the Year' for 2008. She was awarded the State Prize of the Russian Federation (2004).