Fran opened the floodgates with a goal after just seven minutes but his effort was cancelled out by Atletico's Matias Lequi just four minutes later.
Depor took a further 25 minutes to add to their tally when Enrique Romero got on the scoresheet to make it 2-1.
The second half got no better for the visitors as Sergio made it three five minutes after the interval before Walter Pandiani (pictured) scored the fourth six minutes later.
Matters got worse for the visitors with ten minutes remaining when Spanish striker Javi Moreno was dismissed for a second bookable offence and Lionel Scaloni completed the rout at The Riazor on full time.
Villarreal were held to a 1-1 draw at home by Real Zaragoza after taking an early lead at El Madrigal.
Victor took just four minutes to get off the mark, however, Villarreal failed to increase their advantage and were pegged back by Zaragoza on 23 minutes through David Sanchez Villa.
Athletic Bilbao picked up a draw on the road as they travelled to Estadio Manuel Ruiz de Lopera to face Real Betis.
After a largely uneventful first half, Bilbao broke the deadlock two minutes into the second period through Tiko which looked enough for victory until Marcos Assuncao equalised on full time.
La Liga results:
Deportivo 5-1 Atletico Madrid
Real Betis 1-1 Athletic Bilbao
Villarreal 1-1 Real Zaragoza
