The Hatters were forced to defend for much of the contest, but substitute Rendell stunned the Premier League side with just ten minutes remaining as he found himself in the right place at the right time to steer home JJ O'Donnell's low cross.
The unheralded visitors were reasonable value for their success, though, creating a number of opportunities over the course of the contest as they also edged the possession statistics.
QPR were the second Premier League club to be embarrassed at home, as they were beaten 4-2 by League One promotion contenders Milton Keynes Dons.
Rangers manager Harry Redknapp made nine changes to the Loftus Road side and afterwards blamed his second string players for not taking their chance to impress.
The MK Dons went ahead through an Armand Traore own goal, and a mistake from Anton Ferdinand allowed Ryan Lowe in behind the defence to make it 2-0 shortly before half-time. Ryan Harley and Darren Potter then scored similar close-range strikes six minutes apart to leave the West London club 0-4 down in front of their own fans.
Two late goals dressed up the scoreline a bit for QPR, but Rangers were well beaten, and Redknapp will probably just take this as an excuse to dabble in the transfer market.
In a repeat of the 2011 final, Manchester City beat Stoke City 1-0, the Premier League champions dominated the action and finally broke through five minutes from time when Sergio Aguero the chance to play the ball across the area, and Zabaleta arrived at the back post to turn it goalwards.
Olivier Giroud scored twice as Arsenal moved into the last 16 with a 3-2 victory at Brighton & Hove Albion. After a rampant victory over West Ham in midweek, Arsenal needed Theo Walcott came off the bench to seal victory with an 85th minute winner.
John Heitinga also came off the bench to fire Everton to a 2-1 win over Bolton at the Reebok Stadium. The tie looked to be heading for a replay after Marvin Sordell cancelled out Steven Pienaar's opener, but Heitinga pounced on a loose ball in the penalty area to lash home from 12 yards in injury time.
SAT 26 JAN 2013 - FA CUP RESULTSStoke 0-1 Man City
Bolton 1-2 Everton
Brighton 2-3 Arsenal
Derby 0-3 Blackburn
Huddersfield 1-1 Leicester
Hull 0-1 Barnsley
Macclesfield 0-1 Wigan
Middlesbrough 2-1 Aldershot
Norwich 0-1 Luton
QPR 2-4 MK Dons
Reading 4-0 Sheff Utd
Man Utd 4-1 Fulham