Rovers skipper Scott Dann earned a replay as he cancelled out Alvaro Negredo's opener in a game which saw Dedryck Boyata dismissed late on.
Manuel Pellegrini had vowed prior to kick-off that he would be taking the competition seriously, and the City boss was true to his word as he named a starting XI which included the likes of Fernandinho, David Silva and Negredo.
Championship hopefuls Blackburn started positively enough on home soil and had chances to take the lead - through Dann and Chris Taylor - but saw all of their hard work undone on the stroke of half-time.
Edin Dzeko was allowed to glance on an outswinging corner and Spanish hit-man Negredo ghosted around the back post to convert a cushioned volley from close range.
Rovers refused to lie down, though, and hauled themselves level in similar circumstances 10 minutes into the second half, with Rudy Gestede powering a header goalwards from a set-piece which Costel Pantilimon could only spill into the path of Dann to turn home.
A forgettable afternoon for City, in which they were left hanging on at times, ended on a low five minutes from the end when Boyata was shown a second yellow card for upending Blackburn striker DJ Campbell.
City, with a Capital One Cup semi-final against West Ham United coming up next Wednesday, made seven alterations and perhaps paid the price with a loss of intensity.
City's most notable change again came in goal as Pantilimon replaced rested England No.1 Joe Hart.
The reasons were understandable but questions could be asked of Pellegrini's continuing rotation of the two keepers after an indifferent display from the Romanian.
Rovers also made a change in goal, as one of Hart's England predecessors in Paul Robinson returned for his first game for 13 months.
The 34-year-old has now fully recovered after suffering a blood clot on the lung last year and his initial reintroduction was gentle as the visitors made a sluggish start.
Rovers, despite leaving star striker Jordan Rhodes on the bench, were positive and Gestede troubled Joleon Lescott early on.
The frustration for Rovers was that they could not work Pantilimon, with Dann's free header from a corner their best effort but easily claimed.
City slowly began to take control of the game midway through the first half and Robinson twice came out bravely to thwart Negredo.
Fernandinho shot straight at Robinson from outside the box and Silva spurned a glorious chance when he scooped over from a Boyata cut-back.
Rovers pushed again before the break but Gestede failed to connect with a headed chance and Taylor shot over.
City punished them by snatching the lead themselves on the stroke of half-time as Dzeko flicked on a Silva corner and Negredo turned in his 15th of the season.
The manner in which the goal was conceded perhaps led to what seemed a frank exchange of views between Grant Hanley and Taylor as the players left the field at the interval.
Rovers came back fired up and earned reward as they grabbed an equaliser in the 55th minute.
Gestede rose high to meet a Ben Marshall corner with a powerful header and Pantilimon could not hold it. Dann rushed in to sweep past him from close range.
The pace of the game noticeably increased as Taylor put another Blackburn chance over.
Navas came on for Negredo and brought another fine save out of Robinson, who also spilled but re-gathered another effort from Dzeko.
Blackburn were undeterred and sensed an opportunity to pull off a shock.
City's cause was not helped as Boyata upended Campbell to earn his second yellow card.
Rovers poured forward again but the impressive Tom Cairney sent a good shot narrowly wide from distance.
Lescott also needed to scramble back to break up another attack as City clung on.