Cecchinello established the team in 1996 to contest the 125 cc World Championship, initially with Honda machinery. In 1998 the squad recruited two-time 125 cc runner-up Noboru Ueda, who gave the team its first Grand Prix victory at the Malaysian Grand Prix at Johor Circuit in only his second race for the team. Cecchinello himself added a win later that year at the Madrid Grand Prix. Their partnership continued through 1999 and 2000, with Ueda claiming another victory at the 1999 Brazilian Grand Prix.
The team switched to Aprilia for 2001, and Cecchinello took a win with Aprilia at the Catalan Grand Prix. From 2002, LCR expanded into the 250 cc class, signing an Australian rookie named Casey Stoner alongside David Checa. In 2003 Randy de Puniet joined in 250 cc and was in championship contention, ultimately finishing fourth overall with three wins and nine podiums. Stoner, competing in 125 cc, took his first career win with the team that year. At the end of 2003, Cecchinello retired from racing to concentrate on team management.
LCR made its MotoGP debut in 2006 with Casey Stoner on a Honda RC211V. Stoner claimed the team's first pole position at the Qatar Grand Prix in only their second race, and followed it with a podium in Turkey. He finished eighth in the championship before departing for a Ducati factory ride in 2007. Carlos Checa struggled in 2007 with the new 800 cc RC212V, recording a best result of sixth.
Randy de Puniet joined for 2008 and the team ran a single-bike operation for several seasons. In 2009, riding Bridgestone tyres, de Puniet finished third at the British Grand Prix — the team's first premier-class podium since Stoner's 2006 result. De Puniet continued in 2010 before departing, and reigning Moto2 champion Toni Elías took his seat in 2011, finishing fifteenth in the championship.
German rider Stefan Bradl signed for 2012 after winning the Moto2 title and delivered a consistent debut season on the new RC213V, finishing eighth in the championship and winning Rookie of the Year. In 2013 Bradl fought toward the front more consistently, claiming his first premier-class pole at Laguna Seca and his first podium with second place in the race before injury hampered his season.
For 2015, LCR expanded to two bikes, signing Cal Crutchlow on a factory-specification Honda and Australian rookie Jack Miller on an open-specification RC213V-RS.
Miller departed after 2015, leaving Crutchlow as the sole rider. In 2016, after a difficult start, he finished second in Germany before taking LCR's first-ever premier-class victory at Brno — also the first victory for a British rider in the 500 cc or MotoGP class since Barry Sheene in 1981. Crutchlow added another win at Phillip Island, becoming the first British rider to win the Australian Grand Prix. He ended the year seventh in the championship with 141 points.
For 2018, the team re-expanded to two bikes, adding Japanese rookie Takaaki Nakagami. Crutchlow won in Argentina that year and claimed further podiums at Misano and Motegi before a crash in Australia ended his season early. He won the 2019 Americas Grand Prix and claimed three podiums before ultimately retiring after 2020.
Nakagami partnered Álex Márquez in 2021 and 2022, with both riders struggling against the backdrop of Honda's competitive difficulties in those years. Álex Rins joined in 2023 and claimed victory at the Americas Grand Prix, the team's most recent win before Johann Zarco took the 2025 French Grand Prix — a historic result as the first Honda victory since Rins in 2023, and the first French winner at Le Mans since Pierre Monneret in 1954.
Zarco paired with Thai rookie Somkiat Chantra in 2025 before the team transitioned to Zarco and 2025 Moto2 World Champion Diogo Moreira for 2026. Lucio Cecchinello cited the team's continued commitment to Honda as a long-term strategic partnership stretching across three decades of competition.