In singles, Šafářová won seven WTA Tour titles, most notably the 2015 Qatar Open, and reached her highest ranking of world No.

Šafářová also reached the semifinals at the 2014 Wimbledon Championships, and the quarterfinals at the 2007 Australian Open, qualifying for the WTA Finals for the first time in 2015.

Šafářová also competed at the Summer Olympics on three occasions, winning a bronze medal in doubles at the 2016 Rio Games partnering Barbora Strýcová.

[2][3][4][5] Šafářová won her first WTA Tour event in May 2005 at the Estoril Open in Portugal, where she defeated fourth-seeded Li Na in a three-sets final.

At the start of 2007, Šafářová elected to represent the Czech Republic in the Hopman Cup instead of defending her Gold Coast title.

It was the second time in a row that she had beaten Mauresmo in a Grand Slam championship, after winning their only previous encounter in January at the Australian Open.

After failing to qualify for the premier event in Sydney, she reached the third round of the Australian Open by defeating Sybille Bammer and Marina Erakovic before losing to Marion Bartoli in three sets.

Šafářová started into the season by reaching the quarterfinals of the Brisbane International, where she lost to eventual champion Kim Clijsters.

She then suffered first round losses at the Hobart International, where she retired against Kateryna Bondarenko in the third set, and the Australian Open, where she lost to sixth seed Venus Williams.

Šafářová began the year at the Brisbane International where she made it to the quarterfinals after tough matches against Akgul Amanmuradova and Shahar Pe'er where she lost to Anastasia Pavlyuchenkova, in three sets.

Following the Australian Open, Šafářová defeated Daniela Hantuchová in the 2011 Fed Cup, but retired in her second rubber against Jana Čepelová.

She reached the second round in Indian Wells by beating Kristina Barrois, while serving a WTA season-high 18 aces, before losing a close match to 21st seed Andrea Petkovic.

Šafářová was forced to pull out of the Czech Fed Cup tie against Belgium the following week due to a left thigh problem.

However, after beating Johanna Konta, Michaëlla Krajicek, Zhang Shuai, and Petra Martić (after trailing by a set and 4–0), she lost the final to home favourite and world No.

Following wins over Polona Hercog and Simona Halep, she took out eighth seeded Francesca Schiavone to reach her second Toronto quarterfinal.

The following week in the premier Moscow event, she took out second-seed Agnieszka Radwańska in round two before losing to Kaia Kanepi in the semifinals in three sets.

In front of the home crowd at the O2 Arena in Prague, she won her singles match against Angelique Kerber in straight sets, which contributed to a 3–1 victory for the Czech team.

Next, she played for the Czech Republic in the semifinals against France at the Fed Cup, where she beat Caroline Garcia in three sets after saving five match points.

Šafářová began her clay season in Stuttgart where she lost in the second round to eventual finalist Caroline Wozniacki in straight sets, but she would go on to win the doubles title with Mattek-Sands.

Šafářová started her French Open singles campaign by defeating long time friend Anastasia Pavlyuchenkova in two tiebreakers.

She went on to defeat Kurumi Nara and 20th seed Sabine Lisicki, which set up a clash with the defending champion Maria Sharapova in the fourth round.

[16] In doubles she and Mattek-Sands claimed their second Grand Slam title of the year by beating Yaroslava Shvedova and Casey Dellacqua in three sets in the final.

[21] They defeated Sloane Stephens and Madison Keys and then Daria Kasatkina Elena Vesnina to set up a blockbuster meeting with Australian Open finalists Andrea Hlaváčková and Lucie Hradecká, who are known as "The Silent-Hs".

Mattek-Sands and Šafářová prevailed in straight sets,[22] and dominated Chinese pairing Xu Yifan and Zheng Saisai in the semifinals.

Top-seeded in doubles, Šafářová and Mattek-Sands proceeded to the final after winning all their matches in straight sets, but then lost to Caroline Garcia and Kristina Mladenovic.

[28] In doubles, Šafářová and Mattek-Sands won their fourth Grand Slam title, defeating Andrea Hlaváčková and Peng Shuai in the final.

She played for the Czech Republic in the Fed Cup quarterfinals against Spain in a dead rubber alongside Kateřina Siniaková.

At the US Open, Šafářová defeated Anett Kontaveit, Nao Hibino and Kurumi Nara, before losing to CoCo Vandeweghe in the fourth round.

However, on 4 January 2019, she announced that due to body ailments, she would be pulling out of the Australian Open and her farewell tournament would come at a later date.

[41][42] She returned to the WTA Tour at the 2024 Prague Open as a wildcard pair partnering Bethanie Mattek-Sands and reached the final where they lost to top seeds Barbora Krejčíková and Kateřina Siniaková.