The visiting Royals battled to half time without conceding but could do nothing to prevent man-of-the-match Nani opening the scoring with a crisp drive in the 69th minute.
Hard-working striker Javier Hernandez doubled the lead three minutes later and although poor defending allowed Jobi McAnuff to cut the deficit in the final moments, the Red Devils ultimately set up a home quarter-final against either Chelsea or Middlesbrough.
There was less positive news in the form of an injury to utility man Phil Jones, who appeared to damage ankle ligaments early in the game and later left the ground on crutches and in a protective boot.
Ferguson was keen to focus on the positives and said afterwards: "It was a good Cup tie. It ended up a really good Cup tie when they got the goal and had a really good go at it.
"When they got the goal, they then got the ball in the box. We withstood that and I think when you analyse it, we played some great football and should have scored a lot of goals tonight.
"We missed some chances but there were shots saved and I'm really satisfied with the quality of the game.
"A goal can change things and when we got it, we had to defend well. We really should have punished them better, though. At 2-0 you're never comfortable."
On the bustling performance of Hernandez, the Scot added: "15 goals he's got us this season. The great thing about Chicharito is his energy and enthusiasm is fantastic. I thought Nani's contribution was terrific too. I had a feeling he would win the match for us.
"When you look at these draws, you just hope for a home quarter final. You can't ask for any more than that."