And although Bobby Zamora netted a late consolation, a thoroughly unpleasant day for West Ham ended with them slipping out of the play-off spots and the police being called to an unsavoury tunnel fracas.
Coming into this crucial clash, just one place and two points had separated these teams.
It was tight in the table and tight on the pitch and there had been little to choose between the sides until the red-faced Fletcher under-hit a weak 17th-minute back pass that left Stephen Bywater in all sorts of trouble as Nugent easily tackled the exposed goalkeeper before stroking Preston ahead.
Midway through the half, play was bizarrely held up as the referee's assistant curiously received treatment to his flagging arm, but apart from that surreal moment there was to be little else for Upton Park to smile about.
Five minutes before the break, Chris Day was finally forced into his first save of the afternoon when Gavin Williams' corner fell to Fletcher whose low 15-yarder was bravely held by the Preston keeper at the second attempt as Teddy Sheringham slid in.
But just when West Ham looked like rallying, their uphill task took on Alpine proportions in the 43rd minute when Repka senselessly head-butted Brian O'Neil.
Only an offside flag prevented Nugent from ending the contest within seconds of the restart and, just minutes later, the North End scorer was then brilliantly denied by Bywater after Hayden Mullins carelessly mis-controlled.
Alan Pardew had replaced Sheringham with Zamora at the interval and Nigel Reo-Coker entered the fray a little later, but in a tempestuous second half ten-man West Ham never looked like getting back on terms.
Indeed, when Agyemang replaced Nugent with ten minutes remaining, his fresh legs were just too much for a tiring Hammers' rearguard who stood like statues as the North End substitute signalled the end for West Ham when he collected the ball and slotted past Bywater from 12 yards.
Although Zamora volleyed home Marlon Harewood's deep cross with just three minutes remaining, the damage had already been done and when the final whistle blew the police had to dash into the tunnel and seemingly break up the unseemly running battles that had spilled off the pitch.