Leclerc headed every lap of the race in what was a tactical affair, managing his pace to prevent his rivals from using strategy to challenge before sprinting clear in the closing laps.
As such, Piastri remained in contact throughout the red flag-interrupted encounter though never mounted a serious challenge.
At the initial start, Leclerc jumped clear while Sainz went wheel to wheel with Piastri into Sainte Devote.
He picked up a puncture in the process, that would see him stop as he got to Casino Square.
That left Leclerc under attack from Piastri, with Lando Norris third from George Russell and Max Verstappen.
Further back, there was a sizeable crash involving Sergio Perez, Nico Hulkenberg, and Kevin Magnussen as they climbed Beau Rivage.
Perez’s car was left with just one wheel, the other three, rear and front wings have been torn off after he speared hard into the wall on driver’s right, skating back into the path of Hulkenberg who looked otherwise an innocent victim, having locked wheels with Magnussen.
A photographer was also injured in the crash, with Speedcafe confirming with the FIA that they were taken to the medical centre without open wounds before being released soon after in good spirits.
A lengthy stoppage followed during which the field was reset to its original order.
That included the two Alpines, who came together at Portier, an incident that launched Esteban Ocon skyward.
He was retired from the race during the stoppage, the damage to the rear of his Alpine too significant to be repair.
McLaren meanwhile spent the time repairing Piastri’s sidepod and floor, which copped a knock from Sainz in the Ste Devote skirmish.
The race resumed with a standing restart, Leclerc again sprinting into the lead with Piastri second and Sainz third.
It was less combative this time around, the field rounding the opening sequence without issue.
The front four quickly pulled clear of Russell in fifth, who’d been instructed to manage his page.
The Mercedes driver was on the medium tyres, while the four ahead had all swapped tyres – eliminating the need to stop – under the red flag.
After 10 laps, Piastri remained within a second of Leclerc ahead, with Sainz a further second behind in third, Norris having dropped almost two seconds away in fourth.
Russell was falling back quickly, nine seconds away from the front of the race and lapping around a second slower than Leclerc.
Verstappen also failed to challenge, the Dutchman sixth and more than two seconds behind the Mercedes.
The opening third of the race, Piastri appeared to have more pace than he was able to show, but was tucked up behind Leclerc with no path through to the race lead.
Sainz, too, remained in contact despite drifting out of DRS range at points, forcing Piastri to be mindful of defending while also trying to attack.
Leclerc was clearly dictating the pace, keeping the following three cars close by so they couldn’t undercut the race leader.
After 23 laps, the local favourite briefly lit the fuse and set off, opening a 1.2s advantage over Piastri, who in turn inched away from Sainz in third.
However, it remained processional, with nobody up and down the field able to make inroads.
That included Valtteri Bottas who pitted for new hard tyres and quickly caught back up to the back of the pack – setting fastest lap in the process.
Lance Stroll was forced to pit for a second time after he picked up a left-rear puncture, the carcass of the tyre coming off as he entered the lane.
He picked it up by tagging the apex barrier entering the Nouvelle Chicane, limping his way back to the pits as he fell to 16th – the last runner.
Alonso in the other Aston Martin was under intense pressure from Ricciardo, he had been for much of the race, but was offering no way through for the Australian.
At the end of Lap 51, Mercedes pitted Hamilton, prompting Red Bull Racing to box Verstappen next time around.
Both went on to the hard compound tyres, having run their long opening stint on the mediums.
The pair emerged in the same order they’d entered the lane, such was their gap to Yuki Tsunoda in eighth.
Following his stop, Verstappen had pace to burn and quickly reeled in Russell ahead, locking on to the gearbox of the Mercedes on Lap 62.
But while he may have quickly caught Russell, there was no immediate path through and found himself stuck in his wheel tracks.
Ahead, Leclerc continued to hold a small but significant advantage over Piastri, while Sainz had dropped back into the clutches of Norris in fourth.
Like the Russell-Hamilton scrap, the confines of the Monaco street simply afforded him no opportunity to pass.
In the final laps, Leclerc pulled clear, taking an unrivalled chequered flag more than eight seconds clear of Piastri, who’d be caught by Sainz and Norris.
The Australian maintained his composure to finish second with Sainz rounding out the podium from Norris.
Behind them, Russell survived in front of Verstappen, then came Hamilton, Yuki Tsunoda, Alex Albon, and Gasly to round out the points.
Daniel Ricciardo finished 12th, his race spent staring at the rear wing of Fernando Alonso’s Aston Martin.
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