Lotterer is the son of a German-Peruvian father, Henri Lotterer, and a Belgian mother. He was raised from an early age in Nivelles, Belgium, where he began karting at the age of seven, effectively becoming an adopted Belgian.
Lotterer competed in the German and British Formula 3 Championships before being named test driver for the Jaguar Racing Formula One team in 2002. He tested for the team from 2000 to 2003 but was passed over for a race seat when the team selected Mark Webber and Antônio Pizzonia for 2003. Also in 2002, he made a one-off CART appearance for Dale Coyne Racing at the Autódromo Hermanos Rodríguez Circuit, finishing 12th and scoring a point. He also won the Euro F3000 Sprint non-championship event at the Bologna Motor Show in December 2002, driving for Uboldi Corse SRL and defeating Fabrizio Gollin in the final.
From 2003, Lotterer moved to Japan, where he became a mainstay of Formula Nippon (later Super Formula) until 2017. He won the Super GT Championship in 2006 and 2009 with TOM'S, and the Formula Nippon Championship in 2011, accumulating 24 wins across his time in the series.
Twelve years after his testing role with Jaguar, Lotterer made his Formula One race debut in 2014, replacing Kamui Kobayashi at Caterham for the Belgian Grand Prix. He qualified 21st, ahead of teammate Marcus Ericsson, but his race ended after a single lap due to mechanical failure. He declined a subsequent invitation to race at the Italian Grand Prix because the team planned to run Roberto Merhi in the first practice session, contrary to his wish to participate in all available running.
Lotterer made his debut at the 24 Hours of Le Mans in 2009 as a race-week fill-in for the Kolles privateer Audi team. He and co-driver Charles Zwolsman Jr. drove the entire race as a pair after third driver Narain Karthikeyan dislocated his shoulder in a non-racing incident. Driving an Audi R10, they finished seventh overall. That performance earned him a factory drive with Audi Sport for 2010, where he raced the new Audi R15 TDI plus alongside Marcel Fässler and Benoît Tréluyer, finishing second overall.
In 2011, Lotterer, Fässler, and Tréluyer co-drove the newly designed Audi R18. After the Audi works team lost two of its three cars to accidents, the trio held off three works Peugeot 908s to take overall victory by thirteen seconds — Audi's tenth overall win at Le Mans and Lotterer's first.
From 2012 to 2016, Lotterer competed in the FIA World Endurance Championship for Audi Sport Team Joest. He, Fässler, and Tréluyer won the drivers' championship in the series' inaugural 2012 season.
After Audi Sport Team Joest did not return for 2017, Lotterer moved to Porsche, driving the No. 1 car alongside Nick Tandy and Neel Jani. Following Porsche's departure from LMP1 after 2017, he joined Rebellion Racing for the 2018–19 season alongside Jani and Bruno Senna.
Lotterer returned to the World Endurance Championship in 2023 with Porsche's Hypercar programme, partnering Kévin Estre and Laurens Vanthoor in the No. 6 car. He won the drivers' championship for the second time in 2024 alongside Estre and Vanthoor. In December 2024, he joined Genesis Magma Racing alongside Pipo Derani to develop their GMR-001 LMDh prototype.
Lotterer entered Formula E with Techeetah in 2017, partnering Jean-Éric Vergne. He took his first podium at the 2018 Santiago ePrix and finished third at the 2018 Rome ePrix, ending the season eighth with 64 points. In 2019, he claimed his first Formula E pole position at the Rome ePrix and nearly won the Hong Kong ePrix before contact from Sam Bird on the penultimate lap caused a puncture, dropping him to 14th. He finished that season eighth with 86 points; Vergne won the championship for a second consecutive year.
On 17 July 2019, Lotterer joined the TAG Heuer Porsche Formula E Team, partnering Neel Jani. He finished second on debut in Diriyah and secured pole for the Mexico City E-Prix before retiring there. His only podium across the following two seasons was a second place in Valencia in season 7. In 2021, both he and teammate Pascal Wehrlein were disqualified from the first Puebla ePrix after the team failed to declare the race tyres; Wehrlein had crossed the finish line first, while Lotterer had been classified 16th.
Lotterer joined Avalanche Andretti for the 2022–23 season, partnering Jake Dennis. He finished 18th in the championship standings with 23 points, against Dennis's 229 as that season's champion. On 8 September 2023, Lotterer announced his departure from Formula E to focus solely on the World Endurance Championship. He subsequently returned to TAG Heuer Porsche as a test and reserve driver for 2024.
As of 2004, Lotterer resided in Tokyo; he has since moved to Monaco and regularly visits Nivelles and his hometown of Renningen. His interests include cycling, collecting and driving classic cars, photography, and discovering unusual foods. He is close friends with Jean-Éric Vergne and with Allan McNish, the former racing driver turned Audi Sport ABT Schaeffler team principal.
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