The visitors led after 20 minutes when Danny Dichio stroked home a penalty after James Collins had handled.
City responded immediately and Junichi Inamoto headed in at the far post a minute later only for overworked referee Mike Jones to disallow the strike for offside.
The Bluebirds pounded the visitors' goal for most of the second half but were unable to prise open a solid defence in which Matt Lawrence and Darren Ward were outstanding.
City named an unchanged side but Millwall brought in David Livermore and Peter Sweeney.
The game came to life when Lawrence swung a ball to the far post. Dichio headed it back in and the ball stuck the unfortunate Collins on the arm, handing the Lions striker the chance to score from the spot.
With Jobi McAnuff and Richard Langley raiding down the flanks Cardiff kept pressuring the visiting rearguard but a good final ball always seemed to be lacking.
The second half was all Cardiff but they couldn't force the ball home despite numerous chances and all their frustration erupted in the final minute.
Chris Barker and Alan Dunne clashed on the touchline and Dunne then appeared to strike Barker, leaving the referee no option but to issue a red card.
As soon it appeared there was a huge melee in the centre of the field involving all the outfield players.
Once Mr Jones had regained control he showed a second yellow and then a red card to City defender Collins and followed that with a straight red for Millwall's Livermore.
Wise was so incensed on the touchline that he threw a water bottle that struck the referee's assistant and he was also sent from the field off play.
Unfortunately all this came too late to help Cardiff and the defeat means they still have the spectre of relegation hanging over them.