The Minstermen started their rout inside the first two minutes with Josh Carson's 20-yard effort looping over Scunthorpe keeper Sam Slocombe via a slight deflection off David Mirfin.
It was to get even better for the hosts nine minutes later with Wes Fletcher firing past Slocombe from the tightest of angles after a fantastic turn past defender Niall Canavan.
York's whirlwind start continued as they added a third in the 21st minute through Ryan Brobbel. It was Fletcher who this time turned provider with the winger finding the far corner after a neat turn inside Christian Ribeiro.
Brobbel extended City's lead five minutes before half-time with his second of the game as he found the net with a fine volley from Luke O'Neill's cross.
Scunthorpe reduced the deficit one minute after the break with top scorer Sam Winnall guiding the ball beyond York keeper Michael Ingham, but it proved to be scant consolation.