For just the fifth time in the modern MotoGP era, the championship battle will be decided at the final round of the season.
Quartararo trails Ducati's Francesco Bagnaia by 23 points coming into the finale, and needs to win on Sunday and hope his rival is 15th or lower to have any hope of retaining the crown.
The reigning champion is injured coming to Valencia, having fractured the middle finger on his left hand, and several times in FP1 the Yamaha rider was seen stretching his hand on cool-down laps.
Quartararo set the pace early on with a 1m33.439s, taking over from Honda's Marc Marquez.
The pair traded the op spot several times over the opening course of the 45-minute practice, with Marquez leading the way with a 1m31.805s after seven minutes of running.
Around 15 minutes later, Marquez slid off his Honda at Turn 2, but was quickly able to rejoin the session on his number one bike.
With just under 14 minutes to go, Quartararo returned to the top of the order with a 1m31.399s which would go unbeaten through to the chequered flag.
Marquez held onto second, 0.035 seconds adrift of Quartararo, while KTM's Brad Binder completed the top three.
Bagnaia made a steady start to the biggest weekend of his grand prix career, the factory Ducati rider 0.6s off the pace of Quartararo down in 17th.
Jack Miller was fourth at the end of FP1 as he begins his final weekend as a Ducati rider, with Alex Rins fifth as Suzuki begins its farewell round.
Pramac's Johann Zarco headed teammate Jorge Martin in sixth, with Miguel Oliveira eighth as he starts his final round with KTM ahead of Aprilia's Aleix Espargaro and Honda-bound Joan Mir on the sister Suzuki.
Luca Marini was 11th on the VR46 Ducati from Tech3 KTM's Raul Fernandez, Yamaha's Franco Morbidelli and Gresini's Enea Bastianini – the four-time race winner claiming on Thursday that Ducati has not issued any new factory orders in regards to racing Bagnaia this weekend.
Remy Gardner started his final MotoGP weekend 15th for Tech3 ahead of Maverick Vinales on the sister Aprilia, while Alex Marquez trailed Bagnaia in 18th on his LCR Honda from factory counterpart Pol Espargaro and VR46's Marco Bezzecchi.
Cal Crutchlow's final race as an RNF Racing stand-in began with him in 21st from Fabio Di Giannantonio (Gresini), LCR Honda's Takaaki Nakagami and RNF's Darryn Binder – who crashed at Turn 1 with 20 minutes to go.
MotoGP Valencia GP - FP1 results
| Cla | Rider | Bike | Laps | Time | Gap | Interval | |
|---|---|---|---|---|---|---|---|
| 1 |  Fabio Quartararo |
 |
Yamaha | 23 | 1'31.399 | ||
| 2 |  Marc Marquez |
 |
Honda | 17 | 1'31.434 | 0.035 | 0.035 |
| 3 |  Brad Binder |
 |
KTM | 20 | 1'31.470 | 0.071 | 0.036 |
| 4 |  Jack Miller |
 |
Ducati | 22 | 1'31.542 | 0.143 | 0.072 |
| 5 | Alex Rins |
 |
Suzuki | 19 | 1'31.564 | 0.165 | 0.022 |
| 6 | Johann Zarco |
 |
Ducati | 23 | 1'31.684 | 0.285 | 0.120 |
| 7 | Jorge Martin |
 |
Ducati | 20 | 1'31.762 | 0.363 | 0.078 |
| 8 |  Miguel Oliveira |
 |
KTM | 19 | 1'31.775 | 0.376 | 0.013 |
| 9 | Aleix Espargaro |
 |
Aprilia | 18 | 1'31.782 | 0.383 | 0.007 |
| 10 | Joan Mir |
 |
Suzuki | 20 | 1'31.809 | 0.410 | 0.027 |
| 11 |  Luca Marini |
 |
Ducati | 21 | 1'31.874 | 0.475 | 0.065 |
| 12 | Raúl Fernández |
 |
KTM | 19 | 1'31.881 | 0.482 | 0.007 |
| 13 | Franco Morbidelli |
 |
Yamaha | 20 | 1'31.915 | 0.516 | 0.034 |
| 14 | Enea Bastianini |
 |
Ducati | 22 | 1'31.917 | 0.518 | 0.002 |
| 15 | Remy Gardner |
 |
KTM | 19 | 1'31.977 | 0.578 | 0.060 |
| 16 | Maverick Viñales |
|
Aprilia | 18 | 1'31.993 | 0.594 | 0.016 |
| 17 | Francesco Bagnaia |
 |
Ducati | 19 | 1'31.999 | 0.600 | 0.006 |
| 18 | Alex Marquez |
 |
Honda | 19 | 1'32.068 | 0.669 | 0.069 |
| 19 | Pol Espargaro |
 |
Honda | 21 | 1'32.116 | 0.717 | 0.048 |
| 20 | Marco Bezzecchi |
 |
Ducati | 18 | 1'32.159 | 0.760 | 0.043 |
| 21 |  Cal Crutchlow |
 |
Yamaha | 20 | 1'32.274 | 0.875 | 0.115 |
| 22 | Fabio Di Giannantonio |
 |
Ducati | 19 | 1'32.604 | 1.205 | 0.330 |
| 23 |  Takaaki Nakagami |
 |
Honda | 21 | 1'32.982 | 1.583 | 0.378 |
| 24 | Darryn Binder |
 |
Yamaha | 9 | 1'33.969 | 2.570 | 0.987 |
| View full results | |||||||
