Dominic Blizzard fired Plymouth ahead in the 65th minute, beating United goalkeeper Daniel Bentley with a 20-yard shot that deflected up off Michael Timlin.
Southend replied two minutes later as danger man Kevan Hurst latched on to a through ball from substitute Cauley Woodrow.
Argyle central defender Neal Trotman excelled in the first half with two goalline clearances from Bentley denying Plymouth top scorer Reuben Reid.
Reid hooked the ball towards goal from a 17th minute corner and Bentley made a brilliant one-handed diving stop on the goal-line to bat the ball away to safety.
At the other end Ben Coker's 22nd minute free-kick was saved by Plymouth keeper Luke McCormick and from the corner Trotman cleared off the goal-line during a goalmouth scramble.
Five minutes later Hurst lobbed McCormick only for Trotman to clear the bouncing ball off the line.
The half ended with Southend in the ascendancy and targetman Barry Corr headed just wide from Hurst's cross.
The second half started with Southend defender Mark Phillips' deflecting 13-goal Reid's goal-bound shot wide and both sides ended up settling for a point.