Ghiotto entered karting in 2008, winning the KF3 class of the Champions Cup in his debut year. He remained in karts through 2010 before moving to single-seaters.
In 2011 Ghiotto joined Prema Powerteam in the Formula Abarth series, finishing ninth in the Italian standings with one podium and sixth in the European standings with four podiums. A sophomore year with Prema in 2012 improved his results to runner-up spots in both the Italian and European Formula Abarth championships.
Ghiotto moved with Prema into Formula Renault machinery, contesting late-season rounds of Formula Renault 2.0 Alps and Formula Renault 2.0 NEC in 2012. For 2013 he ran full campaigns in both the Alps and Eurocup series, taking a win at Spa and finishing ninth in the Eurocup; in the Alps he scored five wins and finished runner-up to teammate Antonio Fuoco. He also won the main race of the Formula Renault 2.0 Pau Trophy that year.
In 2014 Ghiotto graduated to the Formula Renault 3.5 Series with International Draco Racing, a more powerful category that also served as a stepping stone towards Formula One for some drivers that season.
Ghiotto debuted in GP3 at Spa-Francorchamps in 2014 with Trident, taking pole position on his first appearance but not converting it to points in the four races he entered. He remained with Trident for the full 2015 season, taking five victories but losing the drivers' title to Esteban Ocon by eight points.
Ghiotto graduated to the GP2 Series in 2016 with Trident. After a slow start he claimed his first victory in the Sepang sprint race and finished eighth overall. He joined Russian Time for 2017, winning twice — though one Monza victory was taken away after officials ruled he had exceeded track limits while avoiding contact with Nyck de Vries and Charles Leclerc; the race win was awarded to Antonio Fuoco. He finished fourth in the championship.
In 2018 Ghiotto drove for Campos Racing alongside Roy Nissany, taking four podiums and finishing eighth. The following year, partnered with Guanyu Zhou at Virtuosi Racing, he produced arguably his best Formula 2 season: he won four races, claimed multiple pole positions, and finished third in the championship behind champion Nyck de Vries and runner-up Nicholas Latifi. The 2019 campaign was interrupted by controversy, including a Monaco feature race disqualification and a run of bad fortune in France and Azerbaijan.
In 2020 Ghiotto moved to the new Hitech Grand Prix team alongside Nikita Mazepin, winning the sprint race in Budapest before ending the season tenth in the standings. He left Formula 2 at the end of 2020, though he returned for a one-off appearance at the 2022 Monza round to replace Roy Nissany, who was serving a race ban.
In August 2017 Ghiotto participated in the post-Hungarian Grand Prix test for Williams Martini Racing, his only formal Formula One activity.
In April 2023 Ghiotto was announced as a participant in the Berlin rookie test for the Nissan Formula E Team and confirmed as the team's simulator driver. He drove again during the rookie practice session at the Rome ePrix and took part in the pre-season rookie test ahead of the 2023–24 Formula E season.
In April 2024 Ghiotto signed a two-race IndyCar contract with Dale Coyne Racing with Rick Ware Racing, making his series debut at Barber Motorsports Park and the Indianapolis Motor Speedway road course. He later drove for the team at Road America and Laguna Seca in the same season. He subsequently moved into endurance racing, competing in the 2025 European Le Mans Series and 2025 24 Hours of Le Mans with Inter Europol Competition.
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