Derbyshire struck in the last minute of normal time to leave Kevin Keegan's sorry side without a win in 11 Premier League games and having taken just three points from a possible 33.
However, the result could have been very different had Michael Owen converted one of the several chances that came his way.
Newcastle now have two tough away games at Liverpool and Birmingham City, and they could be in the bottom three by the time Fulham come to Tyneside on March 22.
The game also saw a remarkable bust-up between Habib Beye and Morten Gamst Pedersen over a disputed throw-in, with around a dozen players and staff from both clubs getting involved as the pair grappled on the touchline.
Keegan made just one change from the team beaten so comprehensively by Manchester United a week earlier. Jose Enrique replaced Charles N'Zogbia at left back and Obafemi Martins - who had suffered an ankle injury away at the African Nations Cup - had to settle for a substitute's role.
Newcastle almost got off to the perfect start in the third minute when James Milner reached the byline and pulled the ball back for former Ewood Park favourite Damien Duff, but Andre Ooijer was able to block his shot and the ball ran just wide of goal.
Six minutes later Milner clipped a ball into the box which was headed narrowly over by Alan Smith, without a goal in 28 United appearances.
With 20 minutes gone Pedersen made a well-timed block to deflect a shot from Duff after Owen skipped past defender Zurab Khizanishvili and rolled the ball across the box.
Despite Newcastle's dominance, Blackburn were also creating chances of their own and seconds after Duff was denied, Ooijer headed wide at the other end after being set up by Christopher Samba.
United's best chance yet came ten minutes before the break, when Joey Barton clipped a ball over the Rovers defence and left Owen with just Brad Friedel to beat. He took the ball past his old Anfield colleague and, with the angle narrowing, he sent his effort across the face of goal.
Khizanishvili flashed a header just wide from a David Bentley corner in the 43rd minute and Steve Harper saved superbly from Ooijer on the stroke of half-time.
Neither manager made a change for the second half and United had the upper hand in the early stages, with Smith going closest after turning Samba on the edge of the box and shooting wide.
In the 56th minute it was Owen who almost opened the scoring, with Friedel tipping his header over his crossbar from point-blank range.
After Hughes brought on strikers Derbyshire and Jason Roberts with an hour gone, Owen was again denied by Friedel.
Owen was soon joined up front by Martins, who was given a huge ovation as he ran on after replacing Butt, who appeared to be injured. Keegan sent on N'Zogbia for Duff in the 78th minute.
Arguably the game's biggest talking point came next, with Pedersen and Beye squaring up to each other and sparking a 12-man tussle next to the dugouts, which led to both being booked. The pair were lucky to stay on the pitch.
Worse was to come for Beye and his team in the 90th minute, when Pedersen took possession from a United corner and played the ball upfield to Bentley on the right.
With Beye out of position, he easily found Derbyshire, who had raced upfield. He kept his cool to beat Harper and condemn Newcastle to a fifth home defeat of the campaign.