The Predators won for the first time since clinching a postseason berth on March 28. Pekka Rinne made 24 saves for the win and even had an assist.
Filip Forsberg had a goal and an assist, and Colin Wilson, Roman Josi and Mike Santorelli each scored a goal. Nashville lost captain Shea Weber to a lower-body injury nearly midway through the second period.
Patrick Sharp and Patrick Kane scored for Chicago, which is chasing its third Stanley Cup trophy in six years. Corey Crawford, yanked after one period in Game 1, gave up three goals in 2 minutes, 19 seconds in the third period as Nashville turned a tight game into a rout late.
Game 3 is Sunday in Chicago.
With NHL Commissioner Gary Bettman in the stands, he got to see another packed arena in Nashville with Predators fans keeping the Chicago faithful way outnumbered.
The Predators felt like they only needed to make a few tweaks to their game after outshooting and outhitting Chicago in Game 1. They jumped on the Blackhawks from the start, picking up their first man-advantage 61 seconds into the game. Wilson, who scored two goals Wednesday night, roofed a wrister over Crawford's shoulder for the power-play goal.
Chicago managed only one shot midway through the first, but managed to tie it at 1 when Sharp lifted the puck over a sprawling Rinne at 16:13. But Josi scored on a wrister with 3.6 seconds left in the period for a 2-1 lead.
On the ensuing faceoff, the teams scrapped, with roughing penalties handed out to Andrew Shaw and Bryan Bickell of Chicago and Paul Gaustad and Taylor Beck of Nashville. Gaustad hadn't been out of the box long when he drew a double-minor for high-sticking Michal Rozsival, catching the Chicago defenseman with his stick after pushing him away.
Gaustad is one of Nashville's big penalty killers, and he got help from Rinne getting just enough of Sharp's slap shot late to deflect it off the crossbar.
Replay showed six Blackhawks on the ice during a line change when Kane managed to get the puck alone and tie it with his wrister from the left circle slipping under Rinne's glove midway through the period. Nashville coach Peter Laviolette yelled at officials over the missed call.
Weber apparently got hurt when he was checked at the boards by Chicago forward Brandon Saad, knocking the 6-foot-4 defenseman to the ice. Weber went to the bench and went straight to the locker room favoring his right leg. The Predators took back the lead at 14:54 on a wrister by Smith from in front a few minutes later.
Nashville thought it padded its lead in the minutes of the third when Calle Jarnkrok scored, but officials waved it off immediately for Predators forward Mike Santorelli cross-checking Crawford from behind to the ice.
Forsberg got the scoring started with his first career playoff goal unassisted from the edge of the crease at 12:41 of the third. Smith followed with his second on a breakaway, then Santorelli scored at 15:00 keeping fans on their celebrating.
NOTES: The Predators are 2-7 in Game 2s in their playoff history. ... Crawford is 13-11 in first-round games. ... Sharp has 39 playoff goals in his career, and Kane scored his 38th. ... Chicago center Antoine Vermette was a healthy scratch for a second game.