Karatantcheva is perhaps best known for reaching the quarterfinals of the 2005 French Open, upsetting seven-time Grand Slam champion Venus Williams en route.

In 2004, Karatantcheva began her season at the WTA tournament in Indian Wells, where she defeated Alexandra Stevenson in the first, and upset the 17th seed Magüi Serna in the second round.

In August, she reached the quarterfinals of a WTA tournament in Vancouver, British Columbia, and qualified for the US Open, before losing to eventual champion Svetlana Kuznetsova in the first round.

[citation needed] In 2005, Karatantcheva also won a European club championship in Rennes as a member of the Cherno More Elite team (Bulgarian: Черно море Елит).

[7] On December 20, 2005, the French sports newspaper L'Équipe reported that Karatantcheva had failed a drug test earlier in the year at Roland Garros (after the 1/4 final match against Likhovtseva),[8] and that she had appeared in front of a three-person panel of judges to explain the results.

On 3 July 2006, the Court of Arbitration for Sport denied her appeal to overturn the ban with the argument that said nandrolone was found in concentrations which were inconsistent with the normal levels for that stage of pregnancy.

In the finals, Sesil played a tough three-set match and overcame the eighth seed American Angela Haynes.

Having fended off a spirited challenge from second-seeded Angelika Bachmann in the first round of the main draw, she made light work of subsequent opponents en route to the semifinals, where for the second tournament in succession she was scheduled to play Viktoriya Kutuzova.

Her luck changed however, when, at the end of March, she managed to qualify and reach the final of the $50k event in Latina, losing to Iveta Benešová in straight sets.

In May, she played her first WTA main-draw match since her suspension in Fes, Morocco against Elena Baltacha which she won in straight sets.

Karatantcheva qualified for the Birmingham Classic where she reached the quarterfinals winning five matches in a row, upsetting Yaroslava Shvedova in straight sets in the second round, before losing to second seed Maria Sharapova.

Karatantcheva then played at the $50k event in Grapevine, Texas, where she advanced to the final, losing to eighth seed Kurumi Nara in three sets.

Following her performance in Grapevine, Sesil achieved her best result of the year by winning a $75k tournament, the Goldwater Women's Tennis Classic, in Phoenix, Arizona, the biggest title of her career.

Karatantcheva's recent change in form has propelled her well back inside the top 200 and she established herself as one of the leading Kazakh players.

She opened her grass-court season at Birmingham where she entered the qualifying draw and defeated local girl Francesca Stephenson but fell to Thailand's Noppawan Lertcheewakarn in the final round.

Placed in the Asia/Oceania Zone Group I in Astana, Karatantcheva played with Galina Voskoboeva to beat Rutuja Bhosale and Ankita Raina, securing Kazakhstan's 3–0 sweep over India.

At the Miami Open, she entered the qualifying draw and defeated Anastasia Rodionova in the first round, saving two match points and battling almost three hours before winning.

She returned to the United States to compete in two ITF Circuit events in Albuquerque and Las Vegas, losing in the first round of both tournaments.

Karatantcheva elected to skip all grass court events before Wimbledon, and suffered another Grand Slam defeat, this time at the hands of young Estonian Anett Kontaveit in the second round of qualifying.

She began with a win over Sanaz Marand in the first round and squared off against third seeded Kristina Mladenovic in the second, edging the Frenchwoman in a match that lasted over two-and-a-half hours.

[23] In February, she participated at the Abierto Mexicano where she was defeated in straight sets in the third qualifying round by Lucie Hradecká, but nonetheless reached the main tournament as a lucky loser.

Karatantcheva then eliminated Marie Bouzková, Kiki Bertens and Monica Puig to secure herself a place in the semifinals for the second time in her career.

Despite the setback, Karatantcheva was nonetheless able to stay on course towards improving her ranking by qualifying for the main phase of the Indian Wells Open shortly after that.

Next, at the Family Circle Cup in Charleston, she qualified for the main draw, beating Arantxa Rus and Louisa Chirico along the way, and lost in the first round to ninth seed Samantha Stosur.

[31] Karatantcheva did not manage to reach the main draw of the 2016 French Open, losing to Maryna Zanevska in three sets after taking the first one in the second round of qualifying, for which she was not among the seeds.

[32] Her downturn in fortunes continued in Wimbledon, where she suffered elimination in the first round of the qualifying competition at the hands of Shérazad Reix in a hard-fought match that was decided in three sets.

[33] In the qualifying draw for the US Open, Karatantcheva posted a win in three sets against Rebecca Šramková in the first round, but was then defeated by Elise Mertens in another three-setter.

[36] In September 2017, Karatantcheva won the title at the Red Rock Pro Open in Las Vegas, defeating compatriot Elitsa Kostova in the final by a score of 6–4, 4–6, 7–5.

[40] The qualifying event for the US Open saw a repeat of her previous performances, as Karatantcheva did not get past the first round, being defeated 6–3, 2–6, 6–4 by Italian Martina Trevisan.

[42] Her luck didn't change in the qualifying draw for Wimbledon when she was defeated in straight sets by Romanian Elena-Gabriela Ruse,[43] at her last tournament for years.