Britt Assomobalonga's impressive strike pegged back Plymouth as Southend finished the match with 10 men.
Alex MacDonald slid the ball under Shrimpers goalkeeper Daniel Bentley to give the hosts the lead shortly after the break.
But Assomobalonga beat his marker with a smart turn, raced away down the right and fired the ball in for 1-1.
Paris Cowan-Hall was denied a late Plymouth winner, before Barry Corr saw red for a foul on Darren Purse.
VIEW FROM THE DRESSING ROOM
Plymouth Argyle manager Carl Fletcher tells BBC Radio Devon:
"We played well in the first half and in bits of the second, but I felt it was an opportunity missed.
"Southend will be there at the end of the season. They've won four of their last five games and we knew it was going to be tough. They've got some big players and we played really well today.
"We were working all week trying to get wide men in pockets. We were working on our movement of our strikers down the channels and we worked that well.
"I've got some good players here and a good squad. I'll defend them until I'm blue in the face."
Southend United manager Paul Sturrock told BBC Essex:
"I was disappointed with our first 45 minutes. There was a lethargy about us, we let things bounce, our decision making was poor.
"We had a couple of decent chances, but I think they shaded the first half.
"We looked a much stronger team in the second half. We looked the team most likely to score after we equalised.
"We did look as if we were on the ascendancy, think about the amount of corners we had, and we had a couple of half chances we should have done better with."