In 2002, Kirilenko became one of the youngest winners of the junior tournaments at the Canadian Open and US Open.

In 2002, Kirilenko started participating in WTA events. She began moving up the rankings in 2004, but was set back by an injury. At the 2004 French Open, Kirilenko took the first set off Serena Williams before losing in three sets. She was the runner-up to Nicole Pratt at the Hyderabad Open.

At the end of 2005, she climbed back up the rankings and won her first title in Beijing. On 12 June 2006, she broke into the world’s top 20 for the first time. At the US Open, Kirilenko was seeded 20th and reached the third round, before losing to Aravane Rezaï.

Kirilenko made her debut for Russia at the Fed Cup tournament in April 2006. In the World Group quarterfinal tie against Belgium, she lost her singles match against 2005 US Open champion Kim Clijsters, but partnering with Dinara Safina, won her doubles match against Justine Henin and Clijsters. However, Russia ended up losing, 2–3.

In 2006, Kirilenko was selected to be the face of Adidas tennis gear designed by noted British fashion designer Stella McCartney and played exclusively in it for three years. In 2009, she was replaced by Caroline Wozniacki following the US Open.

In January 2007, she advanced to the third round of the Australian Open, before being defeated by third seed Svetlana Kuznetsova. She then competed in the Toray Pan Pacific Open in Tokyo, where she advanced to the second round, upsetting world No. 15 Shahar Pe’er of Israel, before being defeated by Ai Sugiyama. She then competed in the Dubai Tennis Championships, where she reached the second round, before losing in a close match to Daniela Hantuchová.

At the 2009 French Open, Kirilenko was unseeded in the singles tournament, and lost to Olivia Rogowska of Australia in the first round. In the doubles tournament, Kirilenko and doubles partner Flavia Pennetta of Italy were seeded eighth. They made it to the third round, before losing to 11th seeded Anna-Lena Grönefeld of Germany and Patty Schnyder of Switzerland.

She appeared in the 2009 Sports Illustrated Swimsuit Edition alongside Daniela Hantuchová and Tatiana Golovin in a pictorial entitled “Volley of the Dolls”.

Kirilenko dated fellow Russian tennis player Igor Andreev for several years. They split in 2011.

In November 2011, Russian ice-hockey player Alexander Ovechkin of the Washington Capitals identified Kirilenko as his girlfriend on his Twitter account. On 31 December 2012, Ovechkin confirmed the rumors that he and Kirilenko were engaged. In July 2014, she called off her planned wedding saying in comments distributed by the Russian Tennis Federation that there were “a lot of reasons” behind her decision. Ovechkin had faced questions from Russian media about the relationship when he did not accompany Kirilenko to Wimbledon in June.

Between 2015 and 2017, Kirilenko gave birth to two children, and has since not returned to professional tennis; it is not known for certain whether or not Kirilenko will return to the game, as she has not competed professionally since 2014, and at present she is not ranked by the WTA.

On 24 January 2015, Kirilenko got married but the name of her husband was not revealed until a few days later: she married Alexei Stepanov, reported to be the head of the Committee of Public Services in Moscow.

In July 2015, following a ten-month absence from professional tennis, it was reported that Kirilenko had given birth to a baby boy. In July 2017, Kirilenko gave birth to a baby girl.