But there was no danger of them being over-awed against their illustrious neighbours, who they had never previously met in a competitive match, as captain Jim Bentley volleyed them into the lead after just six minutes.
Danny Pugh levelled for the Championship side, but David Artell netted with six minutes to go to seal an impressive victory.
QPR were dumped out by London rivals Leyton Orient, with Jason Demetriou and Adam Boyd on target in a 2-1 success for the Os.
Ipswich crashed out after losing in a penalty shootout loss to MK Dons, after a dramatic tie ended 3-3 after extra-time
Crystal Palace were held to a 1-1 draw at League Two Bristol Rovers, and crashed out after losing 4-1 in a penalty shootout. Stoke lost out in a shootout at League Two side Rochdale
James Wesolowski's goal after four minutes saw Leicester edge out Accrington.
Burnley survived a penalty shootout against Grimsby, progressing thanks to a 4-2 success after the game had finished 1-1.
Charlton, Norwich, Bristol City, Barnsley, Cardiff, Coventry, Plymouth, Sheffield United, Watford, West Brom and Blackpool all recorded victories to progress.