Patton injured his right knee in the first quarter of Sunday's clash and was sent for scans during the game.
GWS co-captains Callan Ward (calf) and Phil Davis (concussion) also played no part in the second half of the visitors' plucky 15.8 (98) to 3.16 (34) triumph.
But Patton's setback was the most alarming for GIANTS coach Leon Cameron.
The 21-year-old, who will reportedly be the target of a big-money offer from the Western Bulldogs, has a history of knee problems.
Patton, who attracted comparisons to Jonathan Brown in his junior career, had surgery on his left knee in Sweden to treat patella tendinopathy after being taken with pick No.1 in the 2011 draft.
The shortened pre-season limited Patton to seven games in the GIANTS' maiden campaign.
The following year he tore the anterior cruciate ligament in his right knee during round three and missed the rest of the season.
The GIANTS snapped a six-game losing streak with their win over the Demons, the expansion club almost certainly ensuring they'll avoid a third consecutive wooden spoon.
St Kilda remains in the box seat to finish last, but on current form the Demons deserve to.
Rhys Palmer kicked four goals for GWS, while on-ballers Devon Smith (30 disposals, two goals), Toby Greene (29 disposals), Dylan Shiel (25 disposals, one goal) and Adam Treloar (26 disposals) were all influential.
In addition to Palmer, Will Hoskin-Elliott (three goals) always looked threatening in GWS's forward line.
Jack Grimes, returning from a hamstring injury, was substituted off and iced his leg.
Fellow co-captain Nathan Jones (30 disposals) led the Demons in one of their darkest hours, as has been the case far too often in recent years.
The home side failed to kick a goal in the second or third quarter, prompting one fed-up fan among the sparse crowd of 17,218 to audibly ask at the final break: "What do you stand for, Melbourne?"
It is a question coach Paul Roos will struggle with as he picks up the pieces following the side's poorest performance under the man who helped end the Sydney Swans' 72-year premiership drought.
GWS had more run and will to win in the second half.
They had one fit man on the bench, while Josh Hunt, Jeremy Cameron, Lachie Whitfield, Tim Mohr, Stephen Coniglio and Tom Scully were among the injured players left in Sydney.
MELBOURNE 2.4 2.9 2.11 3.16 (34)
GREATER WESTERN SYDNEY 2.1 6.4 10.7 15.8 (98)
GOALS
Melbourne: Kent, Watts, Garland,
Greater Western Sydney: Palmer 4, Hoskin-Elliott 3, Smith 2, Kelly 2, Boyd, Mumford, Shiel, Treloar
BEST
Melbourne: Kent, N.Jones, Tyson, Michie
Greater Western Sydney: Mumford, Palmer, Hoskin-Elliott, Smith, Shiel, Greene, Kelly, Tomlinson
INJURIES
Melbourne: Grimes (hamstring)
Greater Western Sydney: Davis (concussion), Patton (knee), Ward (calf)
SUBSTITUTES
Melbourne: Aidan Riley replaced Jack Grimes in the third quarter
Greater Western Sydney: James Stewart replaced Phil Davis in the second quarter
Reports: Nil
Umpires: Craig Fleer, Simon Meredith, Stuart Wenn
Official crowd: 17,218 at the MCG
