The visitors dominated the opening stages and Izale McLeod cracked an 18-yard shot against the woodwork in the 11th minute.
But Vale improved as Ben Williamson caused problems and Hugill squandered a gilt-edged chance.
Hugill came on in the 30th minute after Tom Pope had been stretchered off with an ankle injury.
MK Dons striker Sanmi Odelusi suffered a head injury in the same incident and was replaced by Brendan Galloway.
Mark Kennedy became the second MK Dons player to rattle the woodwork when his 37th-minute strike hit the crossbar.
Vale’s Carl Dickinson then lobbed a shot against the crossbar and despite all the chances the game remained scoreless at half-time.
That changed less than two minutes after the break when Hugill capitalised on a terrible mix-up between Dons’ goalkeeper David Martin and defender Alan Smith.
Billy Knott lofted a pass down the middle and Hugill got between Martin and Smith to chest the ball down and roll it into an empty net with his left foot from 12 yards.
The visitors did not do enough to earn a point in a far less eventful second half, although Vale goalkeeper Sam Johnson was forced into a fine save from Daniel Powell in the 59th minute.