Carter Verhaeghe, Mason Marchment and Jonathan Huberdeau also scored for Florida, which snapped a two-game losing streak. Aleksander Barkov had three assists and Sergei Bobrovsky made 31 saves for the Panthers.
Both of Ekblad's goals came via the power play and gave him his first career four-point game.
''I thought he had a great game,'' Florida coach Joel Quenneville said. ''He did everything right at both ends. He did a lot of good things. It was one of those nights where he had the magic touch and made a lot of great plays.''
Filip Forsberg had a goal and two assists and Mattias Ekholm, Colton Sissons and Ryan Johansen also scored for Nashville, which has lost two straight. Viktor Arvidsson had three assists and Pekka Rinne made 33 saves.
''It's just urgency in our play,'' Nashville coach John Hynes said. ''That's really what it comes down to. We gave up odd-man rushes, our D were pinching at the wrong time, our forwards had to reload a little bit more.''
The teams finish their two-game series Saturday at Bridgestone Arena.
Ekblad pushed Florida's lead to 4-1 with 1:16 left in the second period with a power-play goal, but Forsberg answered 50 seconds later to pull Nashville back within two.
Nashville appeared to draw within one, two minutes into the third on a goal by Rocco Grimaldi, but Florida challenged the play for offside and a video review erased the goal.
Ekblad's second of the game and eighth of the season came at 9:07 of the third to make it 5-2.
''We always want `D' in the rush,'' Ekblad said. ''(Quenneville) is a big believer and pushes us to do that every night. I've just been trying to move my feet. I say to myself before every game, `Skate, skate, skate,' and it's been working this year.''
Sissons again brought Nashville within two with at 12:40 and Johansen made it 5-4 with 1:13 remaining in the third with Rinne pulled for an extra attacker.
''We came out, we were slow and they were obviously playing way better than us in the first,'' Forsberg said. ''The third, when desperation hits in, we were playing great. We were creating chances. We had a couple of more chances that could have went in.''
Verhaeghe scored the game's first goal at 6:29 of the opening period. It was his eighth.
Marchment made it 2-0 at 9:01 with his first NHL goal. Coming off of the right half wall, Marchment cut into the faceoff circle and snapped a wrist shot between Rinne's pads.
''It was definitely special,'' Marchment said. ''I had a good opportunity to score the shift before that and I tried to go high. This time, I just tried to go low. I was lucky it went in. It was an awesome experience.''
Huberdeau's goal 59 seconds into the second gave Florida a 3-0 advantage. Former Predator Patric Hornqvist skated behind the Nashville net and found an unchecked Huberdeau in front where his wrist shot deflected off of Rinne's chest and into the net on the glove side for his ninth.
Ekholm got Nashville on the board at 12:23 of the second on a one-timer from the right point off of a pass from Arvidsson. Ekholm has four goals in the four games he has played since missing six games with a lower-body injury.
FEELS LIKE THE FIRST TIME
Marchment's first period goal was the second time in two games that Rinne allowed an opponent's first career goal. In Tuesday's game against the Carolina Hurricanes, it was Steven Lorentz.
Florida defenseman Radko Gudas played his 500th career NHL game.
SAROS TO IR
Predators goaltender Juuse Saros was placed on injured reserve Thursday, two days after leaving Tuesday night's game against the Carolina Hurricanes. Early in the first period Tuesday, Carolina's Nino Niederreiter collided head-to-head with Saros behind the Nashville net as Saros was playing a puck. Saros finished the first period but was replaced by Rinne to start the second.
Kasimir Kaskisuo was elevated from the team's taxi squad Thursday and served as Rinne's backup.
Johansen returned to the Nashville lineup Thursday. He missed Tuesday's game after being placed on the NHL's COVID-19 protocol list. Prior to missing the one game on the COVID-19 list, Johansen had played four games since missing the previous seven with an upper-body injury.
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