Second-half goals from Alan Browne and Daniel Johnson either side of a Cauley Woodrow equaliser, delivered the victory.
It was a deserved three points for North End who were the better side and showed plenty of attacking intent.
You could see some of the early work done by Lowe this week on the training pitch transfer to the pitch.
There's obviously work to do but there was plenty of promise from the Lilywhites.
Browne gave PNE a 57th minute after great play from Johnson, before the Tykes pegged them back with Woodrow's leveller from close range eight minutes later.
Their winner came 12 minutes from the end, Johnson meeting a free-kick from substitute Ryan Ledson to score.
Lowe had made five changes to the side beaten at Blackburn, Sepp van den Berg, Patrick Bauer, Andrew Hughes, Johnson and Sean Maguire coming in.
The 3-5-2 formation saw Ali McCann operate at right wing-back, Browne and Johnson driving the midfield forward with Ben Whiteman playing the deeper role in front of the back three.
With two minutes gone Johnson led a North End attack and played the ball out to Josh Earl on the left.
Earl's pass back inside found Johnson who lifted a shot over the bar,.
Emil Riis drove a low shot wide from 25 yards after some space had opened up in front of him.
A purple patch from Barnsley saw them go close with two chances in as many minutes.
In the 17th minute, Carlton Morris saw a header come back off the far post after the ball had get a come over from the left-wing.
Then Woodrow headed over the bar from a good position 10 yards out.
Back at the other end, Hughes met a cross from Whiteman and sent a header wide, Hughes soon after turning provider with a ball into the box which Maguire headed across goal and wide.
With 32 minutes played, Van den Berg slid a fine pass down the right channel for Maguire to chase down the side of the box.
Maguire delayed shooting and when he did get a shot away, a defender blocked it.
A few times before half-time North End worked themselves into promising positions , just a bit of better decision-making needed.
Early in the second half, Daniel Iversen dived to his left to save a low shot from Clarke Oduor.
North End make their breakthrough in the 57th minute with a well-worked goal.
Johnson turned superbly on to a pass 10 yards inside the Barnsley half and drove forward before feeding a pass across the pitch to find Browne's run.
The skipper took it into the box before tucking a right-foot shot between keeper Brad Collins and the post.
It was his first goal since scoring a penalty against Coventry on April 24.
The lead was to last just eight minutes though, as Barnsley pulled level.
A low ball from the left side of goal got a deflection and looped across the box into the path of Callum Brittain.
He miscued his shot as Johnson tried to charge it down but the ball fell to Woodrow who prodded it home from close range.
Ledson and Scott Sinclair joined the action in the 70th minute, replacing McCann and Maguire. Both substitutes were involved in the build-up top the second goal.
It came in the 78th minute, Sinclair fouled by Mads Andersen to the left of the box which earned PNE a free-kick and the Barnsley man a yellow card.
North End crowded the six-yard box but Ledson rolled the free-kick square to Johnson who had peeled away from his marker, the midfielder firing a left-footed shot through a sea of legs into the net from 12 yards.
Four minutes after the goal, a Ledson shot from outside the box caught a deflection and forced Collins to dive and glove it behind.
PNE: Iversen, van den Berg, Bauer, Hughes, Browne, Whiteman, McCann (Ledson 70), Johnson (Potts 90), Earl, Maguire (Sinclair 70), Riis. Subs (not used): Hudson, Cunningham Lindsay, Rafferty.
Barnsley: Collins, Helik, Andersen, Kitching, Brittain, Palmer, Gomes, Styles (Benson 83), Oduor (Iseka 75), Morris, Woodrow (Adevoyejo 83). Subs (not used): Williams, Moon, Vita, Jinadu
Referee: Keith Stroud (Hampshire)
Attendance: 11,106 (798 away)