In her first tournament of the year at the ASB Classic in Auckland, New Zealand, she lost in the quarterfinals to Russian Elena Vesnina 6–3, 0–6, 6–3. She then reached the quarter-finals of the Medibank International in Sydney where she lost to World No. 2 Serena Williams 6–7(5), 6–3, 7–6(3), despite having three match points when serving for the match at 6–5 in the third set. Seeded 11th at the Australian Open, Wozniacki advanced to the third round where she lost to Australian wild card Jelena Dokić 3–6, 6–1, 6–2.
Wozniacki reached the quarterfinals of the Pattaya Women's Open in Thailand but lost to 8th seeded Magdaléna Rybáriková 6–4, 6–1. Seeded first at the Cellular South Cup in Memphis, Tennessee, Wozniacki advanced to the final but lost to the Belarusian teenager Victoria Azarenka 6–1, 6–3. Afterward, Wozniacki and Azarenka partnered to win the doubles title, beating Michaëlla Krajicek and Yuliana Fedak 6–1, 7–6(2) in the final.Wozniacki then took part in the first two Premier Mandatory tournaments of the year in North America. At the BNP Paribas Open in Indian Wells, California, Wozniacki lost in the quarterfinals to eventual champion Vera Zvonareva 6–4, 6–2. At the Sony Ericsson Open in Miami, Wozniacki scored her first wins over 18th seeded Patty Schnyder and the 4th seed Elena Dementieva in the third and fourth rounds respectively. She lost to Svetlana Kuznetsova 6–4, 6–7(5), 6–1 in the quarter-finals.
Wozniacki won her first title of the year on the green clay of the MPS Group Championships in Ponte Vedra Beach. After surviving a tough first round encounter against Samantha Stosur, she then handily dispensed of Virginie Razzano and Daniela Hantuchová in straight sets to reach the semifinals. There she survived four match points against her to defeat Elena Vesnina 2–6, 6–3, 7–6(5). She then defeated Canadian Aleksandra Wozniak (no relation) in the final 6–1, 6–2. Seeded fifth on the green clay at the Family Circle Cup in Charleston, she defeated top seed Elena Dementieva 6–4, 5–7, 7–5 in the semifinals before losing 6–2, 6–4 to Sabine Lisicki in the final.Wozniacki then suffered early exits in her next two tournaments, losing to Marion Bartoli 7–6(6), 6–4 in the second round at the Porsche Tennis Grand Prix in Stuttgart and losing in the third round of the Internazionali BNL d'Italia in Rome to Victoria Azarenka 6–2, 6–2. Wozniacki advanced to the final of the inaugural Premier Mandatory Mutua Madrileña Madrid Open, where she lost to World No. 1 Dinara Safina 6–2, 6–4. This was her best result to-date. Seeded 10th at the French Open in Paris, France, Wozniacki lost to Sorana Cîrstea of Romania, 7–6(3) 7–5. Cîrstea and Wozniacki lost in the first round of the doubles tournament to Maria Kirilenko and Flavia Pennetta, 6–4, 6–4.
her 19th birthday she lost in the final of the Swedish Open 7–5, 6–4 to María José Martínez Sánchez of Spain. In her first hard-court tournament in preparation for the US Open and after receiving a bye in the first round of the LA Women's Tennis Championships, she lost in the second round to Sorana Cîrstea 1–6, 6–4, 7–6(5). At the Cincinnati Masters, Wozniacki advanced to the quarterfinals, falling to Elena Dementieva 6–2, 6–1. In the Toronto she lost in the second round to Zheng Jie 7–5, 6–3. She then went on to defend her title at the Pilot Pen Tennis in New Haven. In the first round she had her first ever double bagel win, 6–0, 6–0 over Edina Gallovits in 41 minutes. In the final of the tournament she beat Russian challenger Elena Vesnina 6–2, 6–4 to win her third title of the season.
In January, she was invited by Hong Kong Tennis Patrons' Association to play in the exhibition tournament Watsons Water Champions Challenge.
On 4 February, she won an $75,000 ITF singles title in Ortisei, Italy, beating the Italian player Alberta Brianti 4–6, 7–5, 6–3. On 4 March, she won the $75,000 ITF tournament in Las Vegas, beating top-seed Akiko Morigami in the final 6–3, 6–2.She obtained a wild card for the Pacific Life Open main draw and made her Tier I debut there. She was knocked out in the second round by Martina Hingis 6–1, 6–3. The two faced each other again on 27 April in Copenhagen for an exhibition match, where Wozniacki again lost 7–6(7), 3–6, 6–2.
She then made the semifinals of the AIG Open in Tokyo in October, her first career WTA Tour semifinal, and as a result became the first Danish woman to reach a WTA semifinal since Tine Scheuer-Larsen at Bregenz in 1986. Wozniacki eventually lost to Venus Williams 6–3, 7–5.
