Vale took the lead when Carl Dickinson forced the ball in from close range, before Michael O'Connor struck from the edge of the area and then saw a free-kick put into his own net by Ben Coker.
Sam McQueen pulled a goal back for the Shrimpers in injury time at the end of the game.
There was still time for visiting striker David Mooney to fire a late penalty over the crossbar.
Vale announced before the match that Cardiff winger Matty Kennedy, 21, had agreed a two-month loan extension with the club.
Kennedy, who played the first 86 minutes of Friday's game, will remain at Vale Park until 26 April.
Port Vale scored three first-half goals to dent Southend's play-off hopes.