The Nelson side had several new faces on show but they made the stronger start and dominated the opening period.
Daniel Hartley provided a series of good crosses from the right wing, the best of which fell to Steve Maden who should have done better when he miskicked from six yards out.
The visitors settled into their stride and the game became a tough end-to-end encounter with the tall figure of Steve Hibbert looking to be the danger man as he benefitted from some good through balls into the home penalty area.
But Nelson stalwart Marc Berry and his defence coped well in the face of some dangerous attacks.
At the other end, Luke Hargreaves and Andrew Smith worked some good shooting positions to test visiting keeper Andrew Jones.
Unfortunately an excellent interchange of passes between Alex Mugan and Steve Maden after 34 minutes came to nothing when the ball ran through to the keeper.
With half time approaching, a flurry of attacks by Maine Road produced two chances for Daniel Self but he failed to find the target with two close range headers.
The second half was closely fought with Nelson producing some strong attacking moves thanks to midfielders Adam Whiteside and Simon Nangle.
Luke Hargreaves set up a great chance for Daniel Hartley with a superb through ball after 50 minutes but keeper Jones saved his dipping shot.
And it was Hargreaves who forced Jones into a good save on the hour after beating Maine Road captain Alex Jay on the edge of the area.
Nelson looked to be getting the upper hand as Smith and Maden combined to force Richard Gresty to concede a corner kick after 76 minutes and, a minute later, Hargreaves' free kick forced a good save by Andrew Jones.
But after 78 minutes, Maine Road took the lead with a slice of luck when Daniel Self's low shot was deflected past Nelson keeper Chris Thompson by one of his own defenders.
Five minutes later, the visitors doubled their lead when Self met a low cross from the left wing to blast home a 12 yard shot.
Nelson still battled on bravely and Simon Nangle was unlucky to see his 25 yard dipping shot knocked away from the top corner by Jones as he collided with the post.
But the Blues were caught out in injury time by a break down the right wing and a low cross which gave James Rothel an easy chance to score Maine Road's third goal from close range.
The scoreline gave a somewhat unfair reflection of the play and Nelson left the field knowing that they had put in a good performance which, on another day, would have earned them at least a point.
With the Blues' next two games at home, manager Alex Mugan will be confident of picking up points.