In the 18th minute, Sebastien Bassong rescued the Magpies when he cleared Derbyshire's effort off the line but a Blackburn goal seemed inevitable and, for the almost mute Newcastle fans, it came with worrying ease.
Samba's darting run outwitted the defence and the French defender headed home from six yards into the bottom-right corner.
The Magpies were sloppy in possession and were being overrun in midfield, and four minutes before the break Blackburn doubled their lead through Santa Cruz's second league goal of the season with the Paraguay striker picking almost the exact same spot as Samba.
We could have scored more - Ince
Newcastle's fans warmly applauded their team back onto the pitch for the second half and the home side repaid the support by halving the deficit within five minutes.
In the 47th minute, Newcastle had a penalty appeal for what appeared to be a Martin Olsson handball turned down but, two minutes later, Nelsen brought down Owen, who had been a peripheral figure in the first half, and the England striker struck his penalty down the centre of goal.
Newcastle were reinvigorated and they should have equalised when Damien Duff followed up his mesmerising run with a menacing cross but Geremi, with the goal at his mercy, let the ball bounce off his knee.
Blackburn, led by the veteran midfielder Tugay, deserve praise for quelling Newcastle who, despite the best efforts of substitute Shola Ameobi and Duff, were unable to get the equaliser they perhaps deserved.
Newcastle interim boss Joe Kinnear:
"We needed to stop feeling sorry for ourselves. We need to get rid of all the issues that are going on - Is the club being sold? Are we bringing back Kevin Keegan? - until it actually happens.
"We need to focus on playing football, it's as simple as that. And they need to play football well. But what has not helped matters, I am told, is that six or seven of the best players are missing.
"On the good side, with the international break coming up we could have four or five of them back."
Blackburn manager Paul Ince:
"It was important in the last 48 hours that we shut that out (Newcastle's off-field problems) and concentrated on what Blackburn Rovers is all about rather than feeling sorry for Newcastle.
"Also, it was a case of who got the first goal. As soon as we got the first goal I felt at ease because I knew the crowd would get on their backs.
"It's not the Newcastle players' fault. They are trying, they are trying really, really hard and I feel sorry for them."
This page is best viewed in an up-to-date web browser with style sheets (CSS) enabled. While you will be able to view the content of this page in your current browser, you will not be able to get the full visual experience. Please consider upgrading your browser software or enabling style sheets (CSS) if you are able to do so.