A rain-reduced match saw the Bulls set a mammoth 302 off 41 overs after Western Australia's top three of Shaun Marsh, Michael Klinger and Cameron Bancroft smashed 69, 128 and 73 respectively.
Queensland's chase started in troubling fashion as Matthew Renshaw and Joe Burns both fell for ducks in the opening two overs.
Skipper Usman Khawaja played a steady hand at the top of the order scoring 81 from 78 balls, however a steady flow of middle order wickets meant the Bulls were always chasing the game.
Neser's introduction at 5-63 in the 16th over meant attack was the only way forward for the Bulls and the Ian Healy Trophy winner proceeded in producing a one-day innings for the ages. His swashbuckling knock of 122 from 81 balls included seven sixes and eight fours.
Neser looked to have given Queensland a hope of snatching the game when he struck a six off the first ball of the final over, leaving 21 to get off five deliveries, however he was then run-out trying to scamper through for a desperate two, with his side eventually falling 11 runs short.
The loss leaves the Bulls' JLT Cup title hope in a precarious position with two wins and two losses to their name, while Western Australia remain the competition front-runners with four wins from four games.
Queensland next meet New South Wales on Friday in what is shaping as a must-win game for both teams.