Scottish striker McCormack broke the deadlock in the 57th minute for his 15th goal of the season at Ninian Park.
McCormack returned following a five-match absence due to a hamstring strain and he proved the difference with a close-range header.
Joe Ledley sealed the win for the Bluebirds with a neat finish after 83 minutes and set last season's finalists on the cup trail again.
Cardiff manager Dave Jones said: "Ross' contribution was absolutely superb and he scored another goal.
"He had been out for a long time and because Michael Chopra went back to Sunderland, we had to play him.
"It's great credit to him to come through the full 90 minutes. I didn't want to play him for that long but Jay Bothroyd had to come off. Peter Whittingham also got 90 minutes under his belt in difficult conditions."
Jones made two changes from the side which defeated Plymouth in the Championship with the fit-again McCormack and Whittingham returning after Chopra and Wayne Routledge ended their loan spells.
But the visitors clearly stated that their main priority is to secure promotion back to the Premier League by making eight changes and resting stars Kevin Doyle, Stephen Hunt and James Harper.
But Reading manager Steve Coppell insisted he had no regrets on fielding an under-strength side.
Coppell said: "I have to do what is right for my club and our future and my agenda is something else.
"Many of our players had not played for a month and I had to find out which players I can and cannot trust for the rest of the season. I learnt a lot about the young players today.
"Of course, I'm disappointed with the result because I thought we were more than capable of doing well here."
Cardiff dominated the opening half but it was the visitors who came closest in the 16th minute when Bobby Convey sliced wide from 12 yards after James Henry's cross.
But the hosts had a strong penalty claim turned down by referee Anthony Taylor 10 minutes later when Andre Bikey appeared to handle Whittingham's cross with Bothroyd lurking.
Reading should have broken the deadlock within 60 seconds of the restart through Shane Long but Cardiff goalkeeper Peter Enckelman blocked out the Irishman's close-range shot following Convey's neat cross.
The Bluebirds opened the scoring just before the hour mark when McCormack took advantage of a disastrous offside trap.
Reading pushed out for offside from Whittingham's deep free-kick but Roger Johnson's late arrival into the box caught the visitors napping.
Coppell said: "We gave them a goal through our own inefficiency and then we were chasing the game.
"We have a routine on free-kick situations but we came undone. With our normal personnel we are better than that.
"It was onside and a mistake so we've got no problem with the first goal."
Then Jones' men made the game safe when Ledley's cool finish beat Adam Federici after a simple one-two with McCormack.