The thre previous meetings between the sides ended 1-1, but with Cowdenbeath chasing third spot, the home side always looked the hungrier of the two.
Cowden should have had the game wrapped up after just 15 minutes. The home side were awarded a penalty in the seventh minute when goalkeeper John Dodds brought down Liam Buchanan in the box. Buchanan himself stepped up and fired woefully wide.
Cowden did find the net just three minutes later to give them the lead. Buchanan beat two men inside the area, and although his shot was saved, Gary Fusco was on hand to score the rebound.
Amazingly, Cowdenbeath were given a second penalty five minutes later when Kris Brash fouled Ryan McCallum, and again it was spurned, this time Paul McHale 's shot being excellently saved by Dodds diving to his right.
East Fife got back into it after 47 minutes when Kris Brash's superb free-kick was fumbled by Andrew Carlin and Steven Nicholas put the ball home.
Cowdenbeath then twice hit the woodwork within a minute through David Williams and Fusco.
McHale's brilliant run and finish restored Cowden's two-goal lead before the visitors made it 3-2 after 64 minutes when Craig Lumsden headed home a corner.
East Fife's Michael Renwick was sent of for stamping on Williams, which all but ended their hopes for a comeback before Cowdenbeath sealed the points with a McCallum header with just two minutes left.