The championship leader, who started on pole despite a crash in qualifying, held off pressure from the 2021 Monaco race winner to extend his lead in the standings.
Though ART’s Pourchaire was running within 0.3s of the Brazilian MP Motorsport driver at times, he was unable to pass the leader despite two safety cars.
Drugovich had extended his lead to three seconds in the first part of the race, before the action was neutralised by a safety car on lap 19, with Amaury Cordeel hitting the barriers at Turn 19.
Despite both having had slow pitstops and being held up at the pit exit by the stricken Van Amersfoort Racing car being wheeled back up the road, the pair resumed racing in the same order.
A second safety car on lap 23 after Clement Novalak found the wall at the Fairmont hairpin, having made contact with Liam Lawson, looked set to present another chance for Pourchaire, but Drugovich held fast.
Though Juri Vips closed in on the pair in the final laps, it was Drugovich who held on until the chequered flag, having won both races last weekend in Barcelona.
Pourchaire, who became F2’s youngest ever winner here in 2021, settled for second, with Vips in third, having passed fourth-placed Jack Doohan in the pits.
Both Lawson (Carlin) and Roy Nissany of DAMS stalled on the grid, forcing them to drop to the back of the pack.
Prema Racing rookie Dennis Hauger made big gains on the alternate strategy in the opening lap, passing Marcus Armstrong (Hitech) and teammate Jehan Daruvala on the run to Turn 1.
He then made it past Enzo Fittipaldi for fifth after the pair ran side-by-side into Beau Rivage.
Hitech’s Vips was closing in on Doohan by lap 5, with the Virtuosi driver struggling for pace, but it was in the pits where the pass took place, emerging in front after the second safety car.
The lead could have swapped hands under the same conditions, but both ART and MP Motorsport suffered slow stops, working to Drugovich’s advantage.
Pourchaire was close to Drugovich heading into the Fairmont hairpin on lap 23, but moments later the safety car was deployed after Novalak and Lawson’s contact in the battle for 12th.
Racing resumed on lap 26, and though Pourchaire cut the gap to just 0.3s in the final laps, he was unable to make the past and repeat the feat of last season.
Lawson was a late retirement, suffering a problem and dropping down the order before retiring on lap 37.
Ayumu Iwasa and Calan Williams came together at Fairmont on the final lap, ending both of their races prematurely as they fought for the final points spot.
Fittipaldi finished in fifth for Charouz, with Armstrong in sixth and Hauger in seventh despite his early charge.
Daruvala took eighth, with Logan Sargeant in ninth and Marino Sato rounding off the top 10 for Virtuosi.
F2 Monaco – Feature race results: