Named after American motorcycle racer Cal Rayborn, Crutchlow had football trials with Coventry City and Aston Villa as a youth before a knee injury redirected him toward motorcycle racing. He won the UK Junior Challenge in 1999 and the Aprilia RS125 Challenge in 2001. After several years in British club competition, he won the British Supersport Championship in 2006.
Crutchlow joined the Yamaha factory team in the 2009 World Supersport Championship, winning the title after a closely fought season against Eugene Laverty. A fourth place at the final round in Portimao was enough to secure the championship despite Laverty winning the race.
He then stepped up to the Superbike World Championship in 2010, taking his first two series wins at Silverstone and finishing fifth overall. His performances attracted the attention of the MotoGP paddock.
Crutchlow joined the Tech 3 satellite Yamaha team for 2011, ending the year in 12th place and winning the Rookie of the Year award. In 2012 he improved significantly, achieving two podium finishes — both third-place results in the Czech Republic and Australia — and finishing seventh in the championship. He raced the 2012 British Grand Prix with a broken and dislocated ankle after initially being told there was no break.
In 2013, Crutchlow had his best season as a satellite rider, achieving four podiums including runner-up finishes in France and Germany, and claiming the first pole position of his career at Assen. He finished fifth in the championship with 188 points as the top non-factory rider, earning a move to the factory Ducati team.
Crutchlow's single season at Ducati was blighted by technical problems and injury. A hand injury sustained in Austin caused him to miss the Argentine Grand Prix — the first time in his career he missed a round. He achieved his only Ducati podium with a third place in Aragon before departing the team, signing with LCR Honda for 2015 on the same day his Ducati departure was announced.
Crutchlow spent six seasons with LCR Honda, his longest stint with a single team in the premier class. In 2015 he finished eighth in the championship. The 2016 season brought his breakthrough — a maiden premier class victory in the wet Czech Republic Grand Prix at Brno, ending a 35-year British drought in the top flight. He followed that with victory at the Australian Grand Prix, his first win in dry conditions, and also the first British rider ever to win the Australian Grand Prix. He finished seventh in the championship with 141 points.
His third MotoGP win came at the 2018 Argentine Grand Prix, again in difficult conditions. He finished seven in the championship that year despite missing the final three rounds through injury. Crutchlow reached the podium in MotoGP for eight consecutive seasons from 2012 to 2019, a remarkable streak that underlined his consistency at the sport's highest level. He and Álex Rins and Johann Zarco are the only LCR Honda riders to have won a MotoGP race.
After losing his LCR Honda race seat to Álex Márquez for 2021, Crutchlow was contracted as a test rider by Monster Energy Yamaha. He made four race appearances as a substitute in 2021, and stepped in for Andrea Dovizioso at RNF Racing for six rounds at the end of 2022 after Dovizioso announced his mid-season retirement. He also made a wildcard appearance at the 2023 Japanese Grand Prix, finishing thirteenth. Yamaha confirmed in September 2025 that Crutchlow would no longer serve as test rider.
In 2026, Crutchlow returned to the MotoGP grid as a replacement for the injured Johann Zarco at LCR Honda, competing at the Italian, Hungarian, Czech, and Dutch Grands Prix.
In early 2017 the RAC awarded Crutchlow the Torrens Trophy in recognition of outstanding contribution to motorcycling in the United Kingdom. His three MotoGP victories, consistent satellite-team competitiveness, and the historic achievement of ending Britain's 35-year wait for a premier class win cement his place among the most important British motorcycle racers of his generation.