By winning in Brno, Crutchlow became the first British winner of a MotoGP race since Barry Sheene won the Swedish Grand Prix in 1981.
The LCR Honda rider was was joined on the podium by Yamaha’s Valentino Rossi and Repsol Honda’s Marc Marquez, who leads the 2016 Riders Championship by 53 points over his Italian rival.
Marquez started the race on pole position - but was immediately put under pressure by the Ducati trio of Andrea Dovizioso, Andrea Iannone and Scott Redding.
Within three laps - the speed of the Ducati’s looked to be too much for the rest of the field, as they opened up an early gap on the rest of the field.
While the Ducatis rose through the field, Rossi faltered early - and dropped as far back as 12th, as the seven-time World Champion struggled to adapt to the wet conditions.
However, at the halfway mark - Andrea Dovizioso had troubles with his bike and was forced to relinquish his lead and enter the pits for a bike swap.
For the next few laps, several teams started to change their strategies and swapped bikes to adjust to the drying track - which allowed Crutchlow to push up the field.
Within a lap, Crutchlow was into the top five and was the fastest rider on track - and he continued to gain on race leader Andrea Iannone by over a second a lap.
On Lap 16, Crutchlow overtook Iannone to take the lead in the race - and with six laps remaining, the British rider looked set to secure his maiden MotoGP win.
Valentino Rossi made the most of a drying track, as he scythed his way through the field and into podium contention when he passed both Marc Marquez and Scott Redding to move into fourth.
Rossi’s podium hopes were given a boost when Iannone’s front-tyre seemed to burst - which saw the Ducati rider slip down the grid and out of the top three, allowing Marquez to rise to third.
Crutchlow finished the race strong - and crossed the chequered flag over seven seconds ahead of Rossi, while Marquez crossed two seconds later.
The Avintia duo of Loris Bas and Hector Barbera finished the race in 4th and 5th respectively, while Aspar Team’s Eugene Laverty finished 6th.
Octo Pramac’s Danilo Petrucci finished the race in 7th, just ahead of Andrea Iannone, who slipped into 8th despite leading for the majority of the race.
The Spanish duo of Maverick Vinales (Suzuki) and Tito Rabat (Marc VDS Honda) rounded out the top ten.
Reigning World Champion Jorge Lorenzo finished the race outside of the points in 17th place.