In 2007, Fognini made some real progress on the ATP Tour, notably when he qualified for the 2007 French Open to make his first appearance in a Grand Slam event.

During the South American clay swing, he reached the quarterfinals of Viña del Mar (defeating second seed clay-court specialist Juan Ignacio Chela in the first round) and the semi-finals of Costa Do Sauipe.

In April 2009, Fognini reached the third round of the 2009 Monte-Carlo Masters as a qualifier, upsetting Tomáš Berdych (after losing the first set 1–6) and 14th seed Marin Čilić (for the loss of only two games).

A remarkable win during this season was against the 13th seed Gaël Monfils at the 2010 French Open by also coming from two sets to love down in a match that spanned two days.

In June 2010, Fognini followed up his vein of good form as he defeated Fernando Verdasco, the 8th seed, in the first round of Wimbledon without dropping serve the entire match.

2 Novak Djokovic in the quarterfinals but, prior to the match, he announced that he had made the "difficult" decision to withdraw on doctors' advice that it would be "dangerous" to play.

At the 2012 French Open, he was once again the subject of much drama, saving two match points while battling past the seeded Viktor Troicki in five sets to advance to the third round for the third successive year.

[12] Fognini began his grass season by reaching the quarterfinals of Eastbourne, defeating fourth seed Bernard Tomic along the way, and falling to eventual tournament winner Andy Roddick in a tight three-set match.

[13] Starting the North American summer outdoor hard-court season by qualifying for both the Toronto and Cincinnati Masters, Fognini went on to reach the third round of the US Open, a career-best performance.

Fognini's run again ended at the hands of crowd favourite Andy Roddick in a dramatic match (in which he notably out-aced the American) in four sets.

He reached his first singles quarterfinal of the season at Buenos Aires, losing to top seed David Ferrer in straight sets (whilst winning the doubles alongside Bolelli).

The next week, Fognini achieved a career-best performance at ATP 500 events with a semi-finals showing in Acapulco, defeating Stanislas Wawrinka along the way and again losing to Ferrer (but this time taking a set).

The start of the European clay season saw Fognini gain another top 20 victory, defeating fellow Italian Andreas Seppi in the first round of the Monte Carlo Masters in a typically tumultuous affair with an almost complete lack of momentum.

[19] Here, Fognini played another amazing match to beat Richard Gasquet, his second consecutive top-10 victory, in straight sets to reach the semi-finals of a Masters for the first time, projecting his ranking to a new career-high of World No.

[23] At the 2013 MercedesCup in Stuttgart, Fognini reached his third career final, defeating top seed and home favourite Tommy Haas en route.

He reached his third tour final in as many weeks at Umag, defeating Thiemo de Bakker, Martin Kližan and Gaël Monfils en route.

[24] At the Asian hardcourt leg, Fognini reached the quarterfinals of Beijing, defeating resurgent veterans Tommy Robredo and Lleyton Hewitt (the latter for the loss of only 2 games).

He reached a career-best performance of the fourth round, defeating Alex Bogomolov Jr., Jarkko Nieminen and Sam Querrey, before falling to three-time defending champion Novak Djokovic.

The following week, he played at the Apia International Sydney as the top seed, but was unlucky to draw defending champion Juan Martín del Potro, who was returning from an eleven-month injury lay-off, in his first match.

[27] Fognini won his first Grand Slam at the 2015 Australian Open doubles alongside Simone Bolelli, with a straight-sets win over Pierre-Hugues Herbert and Nicolas Mahut in the final.

At the German Open in Hamburg, Fognini reached the final, but was beaten 5–7, 5–7 by Rafael Nadal, in a match that lasted 2 hours and 34 minutes and saw 12 breaks of serve in the 24 games played.

At the US Open, after a first round loss to Stefano Travaglia, Fognini was immediately suspended from the tournament for unsportsmanlike conduct, specifically three violations including using misogynistic language towards the female umpire.

Despite having little preparation on hard courts leading into the tournament, Fognini managed to win the title after defeating world number 4 Juan Martín del Potro in the final.

Fognini failed to defend his title in Monte Carlo, but still reached the quarterfinals, beating Miomir Kecmanović, Jordan Thompson and Filip Krajinović before losing to Casper Ruud in straight sets.

At the 2021 Barcelona Open, Fognini was defaulted during his second round match against Bernabé Zapata Miralles for verbal abuse towards a line judge after being called for a foot fault.

[53] He won the Valencia Challenger over Roberto Bautista Agut, a final in which two former top 10 players met for the first time since Guillermo Canas beat Nicolas Lapentti in Montevideo in 2006.

In the beginning of the 2024 clay court season he qualified at the 2024 Grand Prix Hassan II and defeated Hugo Gaston and top seed Laslo Djere to reach the quarterfinals.

[58] Fognini guided Italy into the quarterfinals of the 2013 Davis Cup World Group, defeating Ivan Dodig in the fifth and decisive rubber against Croatia.

[6][71] Fognini's serve is relatively underpowered and hardly a trademark weapon, but he puts emphasis on precision and placement, while also having the ability to hit above 130 mph on occasion.

His tactics usually consist of a serve out wide, drawing a weak return, setting Fognini up to hit a clean winner off the forehand side.