Brentford received a blow before they had even kicked a ball in anger after Thomas Frank admitted that the striker had been left out due to a "lot of transfer interest".
Those who did line up for the Bees were relieved to see Eberechi Eze's free-kick ruled out after the England international had caught Mark Flekken out at the near post.
Referee Samuel Barrott ruled that a foul had occurred in the box with VAR unable to intervene because the official blew his whistle before Eze's effort had nestled in the net.
To rub salt in Palace wounds, Brentford wasted little time in taking the lead through Bryan Mbeumo, with the forward cutting onto his left foot before firing past Dean Henderson.
The Bees kept hold of their slender advantage to the break, but they ultimately saw their lead cut out in the 57th minute when Ethan Pinnock diverted the ball into his own net as he attempted to deal with Daniel Munoz's knockdown.
However, Yoane Wissa ultimately spared Pinnock's blushes, pouncing on Henderson's parry to tap home a 76th-minute winner to clinch Brentford's first competitive win over Palace since August 1977.
BRENTFORD VS. CRYSTAL PALACE HIGHLIGHTS
Olise's disallowed goal vs. Brentford (26th min)
Mbeumo goal vs. Crystal Palace (29th min, Brentford 1-0 Crystal Palace)
Pinnock own goal vs. Brentford (57th min, Brentford 1-1 Crystal Palace)
Wissa goal vs. Brentford (76th min, Brentford 2-1 Crystal Palace)
MAN OF THE MATCH - YOANE WISSA
In our opinion, Wissa edges out his teammate Mbeumo for the Man of the Match award after playing a role in both of Brentford's goals.
The 27-year-old provided the assist for Mbeumo's opener, before he showcased his goalscoring instincts to pounce on Henderson's parry to net the decisive goal.
Wissa's impressive display ultimately helped Brentford offer a real attacking threat despite being without the services of Toney.
BRENTFORD VS. CRYSTAL PALACE MATCH STATS
Possession: Brentford 46%-54% Crystal Palace
Shots: Brentford 9-14 Crystal Palace
Shots on target: Brentford 5-6 Crystal Palace
Corners: Brentford 4-7 Crystal Palace
Fouls: Brentford 6-15 Crystal Palace
BEST STATS
WHAT NEXT?
After getting off to a winning start, Brentford will now turn their focus to a tricky away clash against Liverpool next weekend.
Meanwhile, Palace will attempt to produce a positive response when they welcome fellow London side West Ham United to Selhurst Park on Saturday.