A week after waving away a number of shots on goal in a draw against the Brumbies, the Reds scored all their points through penalties at Lang Park, with flyhalf Quade Cooper coolly slotting the winner in the 75th minute.
It was a cruel outcome for the Blues, who dominated possession and territory only to be denied time and again by a desperate Reds defence.
"A lot of things didn't go right for us tonight ... We still worked hard, we still scrambled," Reds captain James Horwill said in a pitchside interview.
"They're a tough team and I thought we did a really good job there."
Coming off a bye, the Blues were the more inventive of the two sides and troubled the Reds' defence by spreading the ball quickly and wide.
The home side made the most of their few chances, with Cooper converting all three penalty kicks, but the Blues went to the break two points up.
A sustained bout of pressure deep in attack set up Jackson Willison for a try, the inside centre receiving the ball wide and stepping past Reds fullback Jono Lance before planting the ball in the left corner to edge his side 11-9 ahead.
Cooper blew a chance to put his team in front when he shanked his fourth penalty wide of the posts in the 54th minute and it appeared to be a costly miss in a second half of few scoring chances.
Australia scrumhalf Will Genia was heroic in defence, saving a try in the 64th minute when he threw his pint-sized body in the path of Francis Saili to intercept a grubbed a kick behind the line and prevent the charging replacement back from scoring.
The Blues pushed desperately for the line, but had the ball turned over twice in the final three minutes as the Reds held on to take top spot, at least temporarily, from the Brumbies in the southern hemisphere competition.
The Brumbies host Perth-based Western Force in Canberra on Saturday.