Lazio snatched victory with the last kick of the game. Matteo Guendouzi laid it off for Isaksen, who rounded his marker in the box and bent a left-footed stunner into the far top corner from 12 yards.
After the match Baroni was full of praise for Danish youngster.
"He has started to become decisive, and I have always felt that he has been ready to explode on the big stage", said Marco Baroni to Sky Sport Italia.
Lazio received two red cards late in the match, and were outnumbered when Isaksen decided the match and Plzen coach Miroslav Koubek also acknowledged how dangerous Isaksen can be when given the time and space.
"We were careless in the end. Isaksen should have had a double marking. When he went past Vaclav Jemelka, we should have had a player cover for his left foot. We knew how dangerous he can be", says Plzen coach Miroslav Koubek to uefa.com.
Isaksen himself wasn't too happy happy with his own performance despite the goal.
"I am very grateful that the coach (Marco Baroni, ed.) let me play today. I am growing a lot as a player and can feel the trust from the coaches and the team. They help me a lot and I'm happy to reciprocate. Today was not my best game, but I am happy that I was allowed to stay on the pitch."
"A goal is a goal. I would also like to score the less nice ones. I don't care. Most of all, I'm just happy that it went in tonight", he told SportMediaset after game.
Lazio will host the second leg against Viktoria Plzen on Thursday. The overall winner will meet either Norwegian Bodo/Glimt or Greek outfit Olympiakos in the quarter-final of the tournament.