Fognini started his 2015 season at the Hopman Cup, partnering Flavia Pennetta. Italy failed to reach the final, finishing at the bottom of their group. 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. He lost in three sets. 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. He beat Rafael Nadal in the Semi-finals of the Rio Open before losing in the final to David Ferrer. In April, he beat Rafael Nadal again in the third round of the Barcelona Open, but he again lost in the next round to Pablo Andujar. In May, after defeating Steve Johnson and Grigor Dimitrov, he lost to Tomáš Berdych in the third round of the Rome Masters. At the US Open, Fognini beat Steve Johnson and Pablo Cuevas to advance to the third round where he caused a major upset, beating Rafael Nadal in five sets, coming from two sets and a break of serve down in both the third and fourth sets. In that match, Nadal won the first two sets, and previously had been 151–0 in Grand Slam matches that he led two sets to none. Earning 70 winners, Fognini ended up beating Nadal in five sets. He subsequently lost his fourth round match against Feliciano López.