The Hammers wasted no time piling on the agony for Palace and they set about continuing their drive for an instant return to the Premiership.
On ten minutes, Palace keeper Cedric Berthelin needed treatment after bravely slide tackling Mellor on the edge of his area.
As Aki Riihilahti forced David James to fist over his looping header, there was more pain for the Frenchman on 19 minutes as Defoe produced a goal that had all the echoes of Pele's unforgettable Mexico 1970 dummy.
This time, in the rarefied atmosphere of London's East End, the livewire England Under-21 striker raced in pursuit of ex-Hammer Michael Hughes' underhit backpass and as Berthelin skidded out, his feint saw the forward and the ball go either side of the bemused keeper before he slid his eighth goal of the season into the empty net from close range..
Dougie Freedman then squandered a brilliant chance to claw Steve Kember's side level as he sliced wide, while on the half hour mark, the fleeing Mellor was equally guilty at the other end as he drilled his shot against Berthelin's knees.
As the groans rang around Upton Park it looked like the luckless on-loan Liverpudlian was destined never to score for West Ham.
But within seconds he had proved the doubters wrong when he climbed highest at the far post to meet Matthew Etherington's deep cross with an angled, looping header.
Having broken his duck, Mellor was hungry for more. Indeed ten minutes into the second half, he gratefully accepted Riihilahti's stray pass and spread the ball wide before popping up in the six-yard box to tap home Wayne Quinn's pinpoint low centre.
To their credit, plucky Palace refused to wilt and only the agility of James prevented from reducing the arrears, though this was an evening when the Hammers, who also saw Defoe rattle the post late on, simply had too much firepower for the visitors.
West Ham: James, Repka, Dailly, Pearce, Quinn, Lee, Horlock, Etherington, Connolly, Defoe, Mellor. Subs: Bywater, Ferdinand, Alexandersson, Garcia, Kilgallon.
Crystal Palace: Berthelin, Smith, Powell, Mullins, Butterfield, Riihilahti, Hughes, Derry, Johnson, Freedman, Shipperley. Subs: Cronin, Routledge, Borrowdale, Fleming, Symons.
Referee: M Jones (Cheshire)
Attendance: 31,861
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