Tyler Arnason and Brad Richardson scored in regulation for the Avalanche. Jose Theodore made 30 saves and turned aside shots by Selanne, Ryan Shannon and Ryan Getzlaf in the shootout to win a rematch of last season's Western Conference semifinal.
Selanne became the 36th player in NHL history to reach the milestone. He joined Jari Kurri as the only Finnish-born NHL players to score 500 goals.
The 36-year-old Selanne sent a wrist shot past Colorado goalie Jose Theodore at 14:54 of the second period. Andy McDonald set up the goal with a cross-ice pass.
Dustin Penner also scored for the Ducks and Chris Pronger had two assists. Jean-Sebastian Giguere stopped 41 shots and had his shutout streak snapped at 85 minutes, 44 seconds.
Anaheim outshot the Avalanche 12-10 in the third period. Brad Richardson missed an open net at 16:28 of the third for Colorado.
The game was tied 2-2 after two periods.