Jack Payne dinked a shot over goalkeeper Daniel Bentley to put Southend ahead before veteran forward Grant Holt drilled home an equaliser.
Joe Rafferty's first goal of the season put Dale in front and Jamie Allen made it 3-1 with a long-range drive.
Joe Bunney added a fourth to move Rochdale to within two points of the play-off places.
Phil Brown's Southend slip down to 12th, four points adrift of the top six.
Rochdale manager Keith Hill told BBC Radio Manchester:
Media playback is not supported on this device
"We've reached the point of safety when, 10 games ago, we were looking at getting involved in a relegation fight.
"I was really pleased with the equaliser and then the second half.
"The second-half performance just showed our intent."
Rochdale leapfrogged Southend to climb up to eighth place in League One with a comfortable win over the Shrimpers.