The Brumbies survived a second half comeback from the Reds to secure a 20-23 Super Rugby victory in Brisbane on Friday.
The teams also met in Round One in Canberra and the Reds won the match 17-27 so both teams beat the other away from home.
The result provisionally moves the Brumbies to the top of the Super Rugby standings but if the Sharks beat the Lions later in the round the Sharks will overtake them again.
The Brumbies led 3-20 after 31 minutes but the Reds doggedly fought their way back in the second half, dominating territory and possession to get within three points with 11 minutes left.
But the Canberra-based outfit dug in and finished the Australian derby in Queensland's half as the clock wound down.
The victory lifted the Brumbies to a five-point break over the New South Wales Waratahs, who were to play Western Force in Perth on Saturday.
It was a bitter defeat for the Reds and they have now lost their last four games by five points or less.
The Reds will remain in fourth place in the Australian conference, irrespective of this weekend's results.
"We are extremely pleased with the win. It's a difficult place to come and win, the Reds are a good side anyway, but when they play at home they grow an extra leg," Brumbies skipper Ben Mowen said.
"I thought the way we defended in the second half was outstanding in the end."
Stephen Larkham's Brumbies have now won eight of their 11 games in Brisbane and lead the Reds 18-5 overall with one draw.
"We needed to capitalise on things we did earlier in the match, we built some good pressure," Reds skipper James Horwill said.
"That's probably the third or fourth result that we've lost by three points so we need to be better."
The Brumbies started better and scored in the ninth minute when forward Scott Fardy scored after Quade Cooper lost the ball near his line.
The Reds' ill-discipline cost them points and Nic White kicked the Brumbies to a 10-point lead before winger Joe Tomane scored his first try of the season in the 31st minute off a long pass from White.
Queensland pulled back to trail 10-20 at halftime after flanker Beau Robinson scored off a driving maul.
The Reds had the Brumbies under enormous pressure and had a try by Will Genia disallowed on a TMO decision after an infringement and Rod Davies lost the ball in Tomane's tackle close to the Brumbies' try-line.
Cooper was also over the line but lost the ball, before Ed Quirk scored off a dominant scrum, diving on the ball at the feet of the back-pedalling Brumbies' pack.
Cooper kicked his 700th point in Super Rugby with a penalty to nudge the home side to 20-23, but that was as close as they got.
The Brumbies and Reds have a bye over the Easter weekend.
Final Score Reds 20 (10) Brumbies 23 (20)
Tries - B.Robinson, E.Quirk
Pen - Q.Cooper 2
Con - Q.Cooper 2
Tries - S.Fardy, J.Tomane
Pen - N.White 3
Con - N.White 2
Referee: Steve Walsh
Assistant Ref 1: James Leckie
Assistant Ref 2: Will Houston
TMO: George Ayoub
1. James Slipper , 2. James Hanson , 3. Greg Holmes , 4. Rob Simmons , 5. James Horwill (C) , 6. Eddie Quirk , 7. Beau Robinson , 8. Jake Schatz , 9. Will Genia (VC) , 10. Quade Cooper , 11. Chris Feauai-Sautia , 12. Anthony Fainga'a , 13. Ben Tapuai , 14. Rod Davies , 15. Ben Lucas
Replacements : 16. Saia Fainga'a (100th Super Rugby game) , 17. Albert Anae , 18. Jono Owen , 19. Ed O'Donoghue , 20. Curtis Browning , 21. Nick Frisby , 22. Mike Harris/Dave McDuling (debut) , 23. Jamie-Jerry Taulagi
Jesse Mogg, Joe Tomane, Tevita Kuridrani, Pat McCabe, Robbie Coleman, Matt Toomua, Nic White, Ben Mowen (c), Jarrad Butler, Jordan Smiler, Tom Staniforth, Scott Fardy, Ben Alexander, Stephen Moore, Scott Sio.
Replacements : Siliva Siliva, Ruan Smith, JP Smith, Jack Whetton, Lachlan McCaffrey, Michael Dowsett, Andrew Smith, Christian Lealiifano.