Curtis Bateson's second goal of the season got the visitors off to a dream start after eight minutes.
The 21-year-old took the ball around goalkeeper Magnus Norman and slotted home shortly after Ryan Fallowfield struck a post as the visitors seized early control.
Rory McKeown levelled things up six minutes into the second half by tapping in Ben McKenna's low cross, before North Ferriby took complete control.
Connor Oliver put the visitors back in front with a spectacular strike from 25 yards in the 69th minute.
Ryan Kendall made it 3-1 with five minutes remaining and Reece Thompson added further gloss to the scoreline in the 89th minute.
Declan Weeks netted a consolation for the hosts in stoppage time, but the game was long over.
Report supplied by the Press Association
Match ends, Southport 2, North Ferriby United 4.
Second Half ends, Southport 2, North Ferriby United 4.
Goal!  Southport 2, North Ferriby United 4. Declan Weeks (Southport).
Goal!  Southport 1, North Ferriby United 4. Reece Thompson (North Ferriby United).
Ryan Kendall (North Ferriby United) is shown the yellow card.
Goal!  Southport 1, North Ferriby United 3. Ryan Kendall (North Ferriby United).
Substitution, Southport. Declan Weeks replaces Rory McKeown.
Jake Wright (Southport) is shown the yellow card.
Substitution, North Ferriby United. Ryan Kendall replaces Danny Emerton.
Goal!  Southport 1, North Ferriby United 2. Connor Oliver (North Ferriby United).
Goal!  Southport 1, North Ferriby United 1. Rory McKeown (Southport).
Second Half begins Southport 0, North Ferriby United 1.
Substitution, North Ferriby United. Sam Cosgrove replaces Matthew Templeton.
First Half ends, Southport 0, North Ferriby United 1.
Substitution, North Ferriby United. Ross Armstrong replaces Ryan Fallowfield.
Goal!  Southport 0, North Ferriby United 1. Curtis Bateson (North Ferriby United).
First Half begins.
Lineups are announced and players are warming up.
Second-bottom North Ferriby crushed Southport at the Merseyrail Community Stadium.