Sergio Aguero and Edin Dzeko got the goals for the Blues as they wrapped up a second-place finish in the Premier League.
With Reading already relegated and City's UEFA Champions League place assured, the match had a distinct end-of-season feel about it. The match felt like a sideshow to events behind the scenes, with confirmation that first-team coach David Platt would follow Mancini out of the Etihad Stadium coming just before kick-off.
City's travelling support were keen to thank the Italian, with banners held aloft ahead of kick-off and chants in his honour filling the Berkshire air.
On the pitch, City began brightly and James Milner, one of four changes to the side beaten at Wembley in Saturday's FA Cup final, fired over inside two minutes.
Reading started sluggishly and poor defending allowed Aguero a shot at goal moments later, although Alex McCarthy thwarted the Argentinian.
Kolo Toure then pulled up with what appeared to be a knee injury and Maicon's introduction resulted in a defensive reshuffle, with only a fine Joe Hart save preventing Hal Robson-Kanu capitalising with a long-range strike in the 19th minute.
Robson-Kanu blazed over his next attempt, before Hart parried a fierce Garath McCleary drive. Reading were on top and when City did threaten McCarthy was in their way, with a close-range Carlos Tevez header met by a point-blank save.
City were not to be denied for long, though, as an exquisite short corner routine involving Gareth Barry, David Silva and Milner saw the ball played across for Aguero to slot home with power and precision.
Adrian Mariappa blocked a Tevez strike when play returned to the other end, with McCarthy then turning a fizzing Yaya Toure effort around the post before Tevez blazed over.
However, keen not to go down with a whimper, Reading upped the ante for the final 20 minutes and were unfortunate not to net.
Mariappa saw a header well saved by Hart, with McCleary seeing a fizzing drive deflected behind by Joleon Lescott. Tevez cleared a Mariappa header off the line from the resulting corner, before Jem Karacan attempted a 22-yard drive that Hart could only save at full stretch.
Yaya Toure and substitute Dzeko both tested McCarthy in that period, with the latter finally extending City's lead with two minutes remaining. After Reading sloppily gave away possession, Silva slipped through Dzeko, who coolly slotted home a second of the night.