Myskina was born in Moscow and turned professional in 2000, the year in which she broke into the WTA top 500. She won her first WTA title in Palermo in only her second appearance in the main draw of a WTA tournament. She made her debut in a Grand Slam tournament at the US Open and the Fed Cup (playing doubles). In 2000, Myskina scored first career top-20 victory over no. 17 Barbara Schett en route to the Sopot semifinal. She debuted at Roland Garros (which she would later win) and Wimbledon. She played in the Sydney Olympics and reached her first Tier I quarterfinal in Zürich, where she lost to world no. 1 Martina Hingis. Myskina was plagued by injury that forced her to miss the Australian Open. As a result, she fell out of the top 100. She then had a solid indoor performance, reaching the quarterfinals in Leipzig and the semifinals in Moscow, her first career Tier I SF.
2002 was a breakthrough season for Myskina. She scored her first Top 10 win over defending champion Jelena Dokić in Rome, and entered the Top 20 afterwards. Myskina reached back-to-back grass court finals in Birmingham and Eastbourne, and rose to number 15 in the rankings. She won her first Tier II 2002 Brasil Open – Women's Singles title in Bahia, and another runner-up finish in Leipzig confirmed her spot in WTA Tour Championships. She finished the 2002 season in the top 15 for the first time in her career.
Myskina obtained an invite from the Hong Kong Tennis Patrons' Association to play The Hong Kong Ladies Challenge 2003 and reached the Australian Open quarterfinals (her first Grand Slam quarterfinal appearance of six). After claiming the title in Doha and defeating friend Elena Likhovtseva in the first all-Russian final in WTA history, she cracked the Top 10. Established her place among the game elite with a win in Sarasota, Myskina also had mediocre results during the summer season were followed by a quarterfinal appearance at the US Open, back-to-back titles in Leipzig (defeating No.1 Kim Clijsters and No.2 Justine Henin) and Moscow, which was her first Tier I title. She became the first Russian woman to win the Kremlin Cup), and she made the finals in Philadelphia. Myskina qualified for the Tour Championships. She earned more than $US1 million in prize money, and finished the year in the Top 10 for the first time in her career.
2004 was Myskina's best season to date. Myskina successfully defended her Doha title, afterwards becoming the second Russian woman to break into the Top 5, the first was Natasha Zvereva, who rose to number 5 in the World in May 1989. The highlight of Myskina's 2004 season was a victory at the French Open, where she saved match points in the fourth round against Svetlana Kuznetsova, then defeated former world number 1 players Venus Williams and Jennifer Capriati, en route to a 6–1, 6–2 victory over compatriot Elena Dementieva in the first all-Russian Grand Slam final, thus making her the first female Russian to win a Grand Slam singles title. Prior to her French Open victory, she had never made it past the 2nd round at Roland Garros. Following her win in Paris, she rose to No.3 in the rankings. She reached the final in San Diego, breaking Maria Sharapova's 14-match winning streak that included Wimbledon and beat Vera Zvonareva 17–15 in a third set tie-break, saving 9 match points, winning the longest final set tie-break in WTA Tour history. She lost in the 2004 Athens Olympics semifinal to Justine Henin, having led 5–1 in the final set. She rose to a career-high number 2 in the rankings. Myskina recovered from the tough loss to win the Kremlin Cup for the second straight year, and beat number 2 Lindsay Davenport for the first time in 5 meetings en route to doing so. She finished on the top of her group at the WTA Tour Championships, and scored her second win over a world number 1 by again beating Davenport, but lost in the semifinals to the eventual champion Sharapova. Myskina led Russia to its first Fed Cup title, winning 8 out of 9 matches played, including winning all of her 3 matches in the final. Finished the season as world number 3, a career-best year-end rank for a female Russian, and won over $2 millions in prize money, having scored ten Top 10 wins during the 2004 season.
2005 brought Myskina mixed fortunes. She spent the first half of 2005 poorly, due to personal issues regarding her mother's health. Myskina surrendered her Doha and Roland Garros titles in the very first round, and became the first Roland Garros champion to lose in the opening round. Bringing an 8–10 win-loss record to the beginning of the grass court season, Myskina managed to turn it around at Wimbledon by reaching her career-first quarterfinal at the event with three comeback wins over Jelena Janković (from a 1–5 final set deficit), and over Dementieva (being 1–6, 0–3 down and facing match points in the second set tiebreak). She fell out of the Top 10 in August. She then won a tenth career title in Kolkata beating lower-ranked opponents. She did, however, beat the 2005 Wimbledon champion Venus Williams in Fed Cup semifinals, but then lost both of her matches in the final. Myskina finished inside Top 15 for the fourth straight time.
2006 was another disappointing season for Myskina. Having had several chances to return to the Top 10, she failed to convert any of them. In Warsaw, she suffered her worst defeat in terms of the rankings on WTA Tour level, falling to a wild card, Agnieszka Radwańska, then ranked No. 309. At Roland Garros, Myskina defeated 2005 quarter-finalist Ana Ivanovic in the third round before losing to the eventual champion Justine Henin in the fourth round.
She showed splashes of her old form during the grass season, having reached the Eastbourne final beautifully, losing to Justine Henin-Hardenne in a close final concluded in a third set tiebreak. She made the Wimbledon quarterfinals, but lost to eventual champion Amélie Mauresmo in three sets. She had solid performance at the first two Grand Slams, making the 4th round on each occasion. After Wimbledon, her game completely fall apart. Along with second straight runner-up finish at the Tier IV event in Stockholm, she did not manage to win a single match in North America, going 0–3 during the US Open Series. The downfall reached its nadir when she became the first person to lose a Grand Slam match against future World No.1 Victoria Azarenka at the US Open, having entered the event under an injury cloud carried over from New Haven. Anastasia sat out for a majority of the indoor season with a foot and toe injury, pulling out of Stuttgart and her home tournament in Moscow. She returned to play in Zürich, but lost to then unknown Swiss qualifier Timea Bacsinszky, 6–3, 6–3.
Myskina only played two singles matches, having been injured. She lost both of those matches; including to Meghann Shaughnessy at the French Open, only winning a game. As of 25 July 2007, Myskina fell to the same ranking as the wildcard she lost to, Agnieszka Radwańska, of Number 309. She also is unranked for doubles. Myskina is taking time off due to a career-threatening injury.
Myskina dated HC Dynamo Moscow hockey player Aleksandr Stepanov.
In October 2002, Myskina had a series of photos taken for GQ magazine by the photographer Mark Seliger for a spread in the October 2002 edition of GQ, in which one approved photo of her fully clothed was published. After she won the French Open in 2004, some photographs from the shoot, in which she appeared topless, were published in the Russian magazine Medved (Bear). In August 2004, she filed an US$8 million lawsuit against GQ for allowing her topless photographs to appear in Medved without her consent. On 19 June 2005, U.S. District Judge Michael Mukasey, later United States Attorney General, ruled that Myskina could not stop the distribution of the topless photos, because she had signed a release. Myskina had claimed that she did not understand the photo release form and that she was not fluent in English at the time.
Myskina announced that she was pregnant with her first child, due in May 2008. On 28 April 2008 Myskina gave birth to her first child, a boy. In August 2010 she gave birth to a second son. On 3 November 2011 it was reported that she was pregnant with a third son, and she gave birth in March 2012. When she was interviewed about parenting with Tennis.com she said "Being a mother is so different; it’s not that it’s quieter or faster, it’s just different. Being a mom is tough. You understand what’s good for you and the babies, while tennis is just a game. It’s fun because you have a different life when you step on the court but when the baby is sick you go crazy. When I lost a match it was really bad time, now I know it was a great time, so being a mom is tougher."
Myskina's win-loss record against certain players who have been ranked World No. 10 or higher is as follows: