Hantuchová was born in Poprad, Czechoslovakia (now Slovakia) to father Igor, a computer scientist and mother Marianna, a toxicologist. When her parents split up in 2003, Hantuchová's performances temporarily worsened. At Wimbledon that year, failing to convert match points and weeping on court. She also suffered from a weight problem during this period. She was suspected of being anorexic, however Hantuchová denied this. Hantuchová speaks three languages (Slovak, English and German), and was trained as a classical pianist. She is thought to be a perfectionist and puts a lot of pressure on herself during her training. She qualified for university in Slovakia but deferred it to pursue tennis. She appeared in the 2009 Sports Illustrated Swimsuit Edition alongside Maria Kirilenko and Tatiana Golovin in a pictoral entitled Volley of the Dolls.
Hantuchová started the year as the world number 38, being known as a new up-and-coming player, in the Gold Coast where she lost to World No. 7 Justine Henin in the second round in a three setter 1–6, 6–0, 6–3. After reaching the last 16, after qualifying, in Sydney, Hantuchová went on to play at the Australian Open losing in the third round to the second seed Venus Williams 3–6, 6–0, 6–4. After climbing the rankings to world number 26, having competed in Paris and Antwerp (reaching the round of 16 in both), she went into the prestigious Indian Wells event, defeating Justine Henin in the fourth round 6–3 6–3 and Martina Hingis in the final 6–3 6–4.
She was the lowest ranked player of 26th (seeded 18th) to ever win the Tier I event. In Miami and Amelia Island Hantuchová went on to lose surprisingly in the second rounds. She then played in Charleston only to be beaten by again in the second round by 1995 Australian Open and 2000 French Open Champion, Mary Pierce 6–3, 6–4, Pierce being ranked 232. Playing in Fed Cup she won one of her two singles rubbers against Switzerland. Also in the clay season Hantuchová reached the quarterfinals in Hamburg and Berlin losing to Martina Hingis respectively in straight sets and Anna Smashnova 1–6, 6–2, 6–3. Having entered the French Open as the 11th seed and World No. 13 and losing her previous match in Rome in the first round, she beat Cara Black (after losing to her in Miami earlier in the year) only to lose to former champion Monica Seles in straight sets in the fourth round.
Hantuchová started 2003 solidly, reaching the quarterfinals at her first three events in Sydney, losing to Lindsay Davenport 6–4 3–6 7–6(3), Venus Williams 6–4 6–3 at the Australian Open (her third Slam quarterfinal in a row), and Elena Dementieva in Paris 7–5 6–3. Hantuchová reached her first semifinal of the year at her fourth event in Antwerp, losing to Williams again, 6–1 6–4. By then, Hantuchová's ranking was at a career high No. 5. Defending a title for the first time in her career, Hantuchová advanced to the fourth round in Indian Wells, losing to Amanda Coetzer 6–4 6–4. Despite a first round loss to Alicia Molik in Miami, Hantuchová rebounded in the Tier I Charleston event, making her fifth quarterfinal in seven events, losing to Ashley Harkleroad 6–2 6–1.
She made her sixth quarterfinal at her next event in Amelia Island, losing to eventual champion Dementieva 6–0 6–1. Hantuchová went undefeated in first round Fed Cup play against Germany, winning both of her matches. Following Fed Cup, she again made it to the quarterfinals for the seventh time of the year at the Tier I Berlin tournament, losing to Kim Clijsters 6–0 6–3. At the French Open, Hantuchová lost in the second round in a marathon match to Harkleroad again 7–6(2) 4–6 9–7 making 101 unforced errors, leading to long-time coach Nigel Sears criticising her attitude publicly.
Following the match, her extremely thin physique was noticed for the first time publicly and some wondered about Hantuchová's health. Kicking off the grass season in Eastbourne, Hantuchová lost in the quarterfinals to Conchita Martínez, but more famously she lost in the second round of Wimbledon to Shinobu Asagoe 0–6 6–4 12–10, with Hantuchová breaking down crying during the latter stages of the match in the midst of making 57 unforced errors. Some theorized that the media's continued interest regarding her weight and the pressure of success at 19 years of age, in addition to her on-court breakdown and her parents' divorce, her coach walked out during the middle of the match.
Hantuchová began the 2009 tour by participating in the Brisbane International as the tournament's fourth-seeded player. She was upset in the first round by Sara Errani 6–7(1), 6–4, 6–0. Hantuchová then played the Medibank International in Sydney where she lost in the second round to sixth-seeded Agnieszka Radwańska.At the Australian Open in Melbourne, the first Grand Slam event of the year, Hantuchová was seeded nineteenth and defeated home favourite Casey Dellacqua in their first round match 7–6(11), 6–4, she then beat Mathilde Johansson of France in the second round before losing to fifteenth-seeded Alizé Cornet of France in the third round 4–6, 6–4, 6–2. In the doubles competition,
Hantuchová and her partner Ai Sugiyama made it to the final, where they lost to Serena Williams and her sister Venus Williams. Hantuchová started the 2010 tour by competing at the Brisbane International. Seeded fourth, Hantuchová was upset by unseeded Andrea Petkovic in the quarterfinals 6–4, 6–2. At the Medibank International in Sydney, Hantuchová fell to No. 5 seed and eventual champion Elena Dementieva in the second round 6–2, 4–6, 6–2. Seeded 22nd at the Australian Open, Hantuchová fell to 16th seed and eventual semifinalist Li Na in the third round 7–5, 3–6, 6–2. Hantuchová defeated Zhang Shuai 6–0, 6–1 in the Fed Cup tie against China in Bratislava, Slovakia prior to the Dubai Tennis Championships in Dubai, UAE. In Dubai, Hantuchová upset No.5 seed Dementieva through retirement after winning the first set 6–4. However, she fell to Anastasia Pavlyuchenkova in the third round 6–3, 6–4.
Hantuchová was seeded No. 2 at the Monterrey Open in Monterrey, Mexico. She became one of the favorites after No. 1 seed Jelena Janković fell in the first round. Hantuchová fought from a set down to beat unseeded Vania King 2–6, 6–2, 6–1 in the quarterfinals and No. 4 seed Dominika Cibulková 4–6, 6–3, 6–0 in the semifinals. However she fell to No. 3 seed Anastasia Pavlyuchenkova in the finals 1–6, 6–1, 6–0. It was Hantuchová's first final since Linz in 2007. Hantuchová was upset at the BNP Paribas Open by Roberta Vinci in the second round after injuring her back during training earlier that day. At the Sony Ericsson Open she gained a career best in Miami reaching the fourth round after recording straight set victories over Patty Schnyder and No. 16 seed Nadia Petrova, but lost a very tight three set match to No. 3 seed and eventual finalist Venus Williams 1–6, 7–5, 6–4 in nearly three hours.
Hantuchová withdrew from her first tournament of the year at the Brisbane International due to a left Achilles strain. She was healthy enough to compete at the Medibank International Sydney but suffered a loss to María José Martínez Sánchez in the first round 6–2, 6–4. At the Australian Open she was the 28th seed, but lost in the first round to Regina Kulikova in an epic three-setter, 7–5, 3–6, 9–7. This is the first time Hantuchová has lost in the first round of the Australian Open, bar her first appearance.