Nashville learned during the afternoon it would have home-ice advantage in the opening round of the playoffs no matter what happened against the Avalanche, but the Predators still put on an offensive show.
Nashville will meet Detroit in the first round of the playoffs, having finished the season with two more points than the Red Wings.
Smith snapped a 1-1 tie with 7:50 left in the opening period and his goal was followed by those of Patric Hornqvist, Roman Josi, Brandon Yip and Matt Halischuk.
Anders Lindback made 34 saves on 35 shots before he was shaken up by players collapsing on him in front of the goal. Pekka Rinne came in to finish the contest.
Jean-Sebastien Giguere stopped 23 shots for Colorado, which will sit out the playoffs for the second straight year and for the third time in four years.