[3] She has previously driven for Amlin Andretti in the 2015/16 season of the FIA Formula E Championship as well as several years competing in the IndyCar Series.

De Silvestro participated in an IndyCar Series test over 8–9 December 2009 at Sebring International Raceway, a joint effort between HVM Racing and Team Stargate Worlds.

After a crash at the Milwaukee Mile during qualifying, de Silvestro was cleared to drive in the race, but withdrew after experiencing dizziness and impaired vision.

[9] De Silvestro missed round 13 of the season at Sonoma, after being refused entry to the United States.

On several occasions the car was black flagged for failing to maintain the minimum safe speed, including the 2012 Indianapolis 500.

On 30 October 2012, de Silvestro signed on with KV Racing Technology for the 2013 IndyCar Series season, driving the No.

De Silvestro joined veteran driver Tony Kanaan to make KV Racing Technology a two-car team for the 2013 season.

[13] De Silvestro finished fourth in the second race of the season, the Indy Grand Prix of Louisiana.

On 19 January 2021, Paretta Autosport announced they would make their Indycar debut at the 2021 Indianapolis 500 with de Silvestro as the driver in the no.

[18] On 15 June 2015, it was announced de Silvestro would drive for Andretti's Formula E team at the championship's double-header finale in London.

In 2016, de Silvestro became the first female driver to score points in Formula E with a 9th place in the 2016 Long Beach ePrix.

De Silvestro returned to the driving seat for Venturi Racing at the December 2018 Ad Diriyah test, where up to nine women took part.

On 5 September 2016 it was announced that she had signed a three-year contract as a full-time driver for Nissan Motorsport in the Australian Supercars Championship, beginning from the 2017 Series.

De Silvestro will compete in the 2023 Repco Bathurst 1000 as a wildcard entry for team Dick Johnson Racing.