Barnsley started off well with their best spell falling within the first quarter of an hour.
Tommy Wright's sixth minute header from a Bobby Hassell cross flew just inches over the crossbar.
Martin Devaney caused the Vale defence more problems three minutes later when he tricked his way past George Abbey and George Pilkington down the left to force a good save from Mark Goodlad.
The home side finally steadied the ship and threatened for the first time after 15 minutes when Sam Togwell set Michael Husbands free but Nick Colgan stood strong and saved the forward's shot.
Husbands took centre stage again after 24 minutes when his 50-yard dash created room but he unselfishly spread the ball to the right of the box where Danny Sonner was waiting to slot the ball home from 12 yards.
With Barnsley's flat defending already exposed, Vale ran riot again in the 27th minute when Togwell's ball over the top allowed Leon Constantine to strike a weak shot that somehow crept underneath Colgan's body.
Barnsley clawed a goal back through Jacob Burns 11 minutes after half-time when he squeezed a powerful low drive through the crowded box into Goodlad's bottom right corner.
The Tykes continued to seize control and pulled level in the 67th minute when Goodlad's parry off a Wright header gave Matt Carbon the perfect chance to tap in from close range.
However, Vale didn't lie down and when Michael Cummins' 25-yard shot looked to be going wide, Togwell stepped in to divert the ball past a helpless Colgan in the 73rd minute to give his side the points.