Chesterfield defender Janos Kovacs was shown a straight red card by the referee in the 51st minute for deliberate handball when he blocked Eastwood's goalbound shot.
The decision stunned the home side and Eastwood put away the penalty to launch a Southend revival that finally saw them come out on top in a seven-goal thriller.
Chesterfield overcame the loss of Kovacs to regain the lead but Southend showed why they are League One leaders by hitting back to win the game with another Eastwood special.
Chesterfield will feel hard done by and they deserved to lead 1-0 at half-time with Colin Larkin giving them a 27th minute lead from close range after a near post corner was flicked across the face of goal by Mark Allott.
But once Eastwood had levelled with a firmly-struck spot-kick down the centre of Barry Roche's goal the match burst into life with the visitors going in front for the first time in the 56th minute.
Eastwood got the ball out on the Southend left before cutting infield and going past four challenges before unleashing a right-foot shot from the edge of the area that swerved and dipped over Roche.
Chesterfield responded by bringing on Caleb Folan and the substitute set up the leveller in the 63rd minute with a neat turn and cross that saw Derek Niven smash a right-foot shot home from 12 yards.
Two minutes later Kevan Hurst produced a piece of individual brilliance to put his side in front when he cut inside before drilling a right-foot shot past Darryl Flahavan from inside the box.
Southend looked stunned but they recovered and were back on level terms when a corner was flicked on at the near post and Shaun Goater headed home from point-blank range.
Eastwood was booked for dissent shortly afterwards but he had the final word with another spectacular effort to win the game.
When Southend were awarded a free-kick 20 yards out, Eastwood sent the ball swerving over the defensive wall and into the top right-hand corner via Roche's right hand. It was a wonderful goal and Eastwood could have had a fourth when James Lawson put him in but this time Roche denied him.