Lee Hughes scored twice on his home debut after the visitors saw Charlie Barnett sent off in the fourth minute for a poor challenge on Daniel Jones.
Hughes volleyed home before Darren Purse, also on his Vale Park debut, turned home a free-kick. Hughes then secured the win with his second goal in the 66th minute.
Cheltenham moved into third place with a 2-1 win over Torquay, while Burton slipped out of the top three after they were reduced to 10 men and drew 1-1 against AFC Wimbledon.
Zander Diamond was sent off in the 76th minute after Michael Symes had cancelled out Wimbledon's lead, courtesy of Gary Alexander.
Rotherham climbed up the table as they beat Northampton 3-1. Daniel Nardiello, Ben Pringle and Michael O'Connor scored for the home side before Clarke Carlisle netted a consolation goal for the Cobblers.
Morecambe eased to a comfortable 4-1 win over York on their first ever visit to Bootham Crescent and Rochdale drew 1-1 with Chesterfield after Bobby Grant scored the equaliser for the home side before being sent off.
Southend beat Oxford 1-0 thanks to substitute Ryan Leonard's 85th minute score.
Meanwhile, Fleetwood drew 2-2 against Bradford at Highbury. Alan Goodall headed the home side into the lead in the first half before scores from Nahki Wells and Ryan Dickson saw the Bantams edge ahead, but the points were shared when James Hanson was adjudged to have handled the ball, with Jon Parkin levelling from the penalty spot.
Elsewhere, Exeter drew 0-0 against Aldershot while Plymouth's game against Dagenham and Redbridge was also goalless.