She turned professional in 1999 and had her breakthrough year in 2002, when she won her first WTA Tour title at the Indian Wells Open, defeating Martina Hingis in the final and becoming the lowest-ranked player to ever win the tournament.

At the Zurich Open, she won three qualifying matches, beat Meghann Shaughnessy and Barbara Schett and lost to eventual winner Lindsay Davenport in the quarterfinals.

In the mixed doubles, she and partner Kevin Ullyett also reached the final, where they beat Gastón Etlis and Paola Suárez, securing Hantuchová her second Grand Slam title in as many years.

25, defeating Tatiana Poutchek, Barbara Schett, Justine Henin, Lisa Raymond, and Emmanuelle Gagliardi en route to the final, where she beat world No.

The following month at the Miami Open, the Amelia Island Championships and the Family Circle Cup, Hantuchová lost in the second round, to Cara Black, Janette Husárová, and Mary Pierce, respectively.

She and Vicario reached the doubles final of both, losing in Hamburg to Martina Hingis and Barbara Schett and in Berlin to Elena Dementieva and Janette Husárová.

She then went on to reach the quarterfinals of Zurich, losing to eventual champion Patty Schnyder in three tight sets, and the semifinals in Linz, and winning both of her singles rubbers in the Fed Cup final.

At the French Open, Hantuchová lost in the second round in a marathon match to Harkleroad again, making 101 unforced errors, leading to long-time coach Nigel Sears criticising her attitude publicly.

Further signs of the pressure and problems she was facing during this period was that, in July, she made herself unavailable for Slovakia in the Fed Cup in order to concentrate on her singles career, and in November she parted company with Sears.

[23] 2004 proved to be a continuation of Hantuchová's poor second half of 2003, with many of the same struggles (she briefly hired Harold Solomon, who had previously coached her friend Jennifer Capriati, as well as Anna Kournikova, before re-hiring Sears in March),[24] She reached just three quarterfinals, the first at the first Tier-I event in Tokyo was not until halfway through the season.

After a second-round loss in San Diego to Sugiyama, Hantuchová reached her fourth final in Los Angeles, getting a walkover in the quarterfinals over Sharapova, and got revenge against Dementieva in the semifinals.

She continued this form at the Australian Open with her third-round victory over defending champion and seven-time Grand Slam winner Serena Williams, who had entered the tournament with a lack of match practice and questions over her fitness.

Despite disappointing results in the warm-up tournaments, she reached the fourth round of both the French Open and Wimbledon, before extending her 2006 Fed Cup record to 6–0 by winning both her singles matches in Slovakia's 5–0 rout of Thailand, which ensured their promotion to the World Group II.

Hantuchová once again fell out of the top 10, after losing in the second round of the Tier-II Pilot Pen Tennis tournament in New Haven to eventual runner-up Ágnes Szávay.

Playing in the Fed Cup World Group play-offs, Hantuchová defeated Alizé Cornet in the first-round rubber, but lost to Amélie Mauresmo in her next match.

Her fourth event was the Warsaw Open, where she reached her second career clay-court semifinal, but lost to Romanian qualifier and eventual champion Alexandra Dulgheru.

She defeated Meghann Shaughnessy, Timea Bacsinszky, and Vania King, but fell in the fourth round to second seed and defending champion Serena Williams.

Partnering Agnieszka Radwańska, she reached the semifinals in Indian Wells, falling to the eventual champions, but won the doubles title in Miami, defeating Nadia Petrova and Liezel Huber.

[37] Hantuchová reached her second career grass-court final at the Birmingham Classic, upsetting second seed Ana Ivanovic in the semifinals, before falling to unseeded Sabine Lisicki.

After a first-round loss at the US Open to Pauline Parmentier, Hantuchová reached the quarterfinals of the Bell Challenge and the Ladies Linz losing to Marina Erakovic and top seed Petra Kvitová, respectively.

Had a great start to the season, making the final in Brisbane, winning in Pattaya and feeling very good about my game, but unfortunately, suffered a fracture stress... that kept me away from the tracks for two months."

[42][43] Hantuchová started her year off in January with a quarterfinal appearance at the Brisbane International, beating Lourdes Domínguez Lino and fifth seed Sara Errani, before losing to Lesia Tsurenko.

Hantuchová's next tournament was the Qatar Ladies Open, where she beat Laura Robson and Ekaterina Bychkova, losing in the third round to sixth seed Sara Errani.

At the Madrid Open in May, Hantuchová received a wild card and beat Sloane Stephens and eighth seed Kvitová, before losing to Kaia Kanepi in the third round.

Hantuchová then suffered two first-round defeats, at the Internationaux de Strasbourg, where she was seeded eighth, to María Teresa Torró Flor, and then at the French Open, to Jelena Janković.

She and Arantxa Parra Santonja beat Darija Jurak and Megan Moulton-Levy in the first round of the doubles, but lost to fourth seeds Raquel Kops-Jones and Abigail Spears in the second.

In doubles, she and Arantxa Parra Santonja won the first round over Daria Gavrilova and Xu Yifan, but lost against Paula Kania and Kateřina Siniaková.

Hantuchová played her 17th singles final at the Thailand Open after wins over third seed Zarina Diyas, Zheng Saisai, Duan Yingying, and Marina Erakovic.

Having fallen out of the top 100 for the first time since March 2002, Hantuchová successfully made her way through qualifying at the French Open, defeating seventh seed Anna Tatishvili, Barbora Štefková and Jennifer Brady.

She first endorsed Babolat from the time she was a junior until late 2003, then Yonex until the 2007 Pan Pacific Open in Tokyo, when she started using the Prince Ozone Seven at the 2007 Dubai Tennis Championships.