Joao Felix opened the scoring in the 23rd minute after he flicked a ball towards Mykhaylo Mudryk, who ran with the ball towards the box from the left before Felix struck past goalkeeper Bartlomiej Dragowski into the right of the net after receiving a return pass.
Mudryk scored himself early in the second half thanks to Pedro Neto, who darted down the right flank and lofted a cross to the back post for Mudryk to head home, and the Ukrainian then set up Felix for his second of the night when his deflected strike fooled Dragowski in the 55th minute.
Christopher Nkunku scored just four minutes later from the penalty spot, though Facundo Pellistri managed to pull one back for the hosts in the 69th minute.
The result means that the Blues are now in first place with six points from their two games in the competition, and are one of only six teams so far to have maximum points after two matches.
As for Panathinaikos, they have one point after two matchweeks and are in 24th place in the Conference League table, and occupy the final round of 16 playoff spot.
Felix was instrumental in the buildup to his first goal given he was able to pin Panathinaikos' backline before he flicked the ball with his head towards Mudryk, who will be pleased that he was able to impact proceedings in the final third considering the fact he has struggled so far at Chelsea.
Neto was key to the Blues's second goal, with his electrifying pace on full display when he charged down the right and created enough room to cross to Mudryk.
Chelsea's third was admittedly fortunate given Felix's strike too an enormous deflection, but Mudryk combined with the Portuguese excellently to help set up the goal in the first place.
Nkunku's penalty put the result beyond doubt, and meant that Pellistri's goal for Panathinaikos was little more than a consolation.
PANATHINAIKOS VS. CHELSEA HIGHLIGHTS
Joao Felix goal vs. Panathinaikos (23rd min, Panathinaikos 0-1 Chelsea)
Joao Felix needed that goal! The forward pins Panathinaikos' backline deep in their half and flicks the ball towards an onrushing Mykhaylo Mudryk, who drives towards the box from the left, passing across to Felix in the penalty before the Portuguese attacker pokes past goalkeeper Bartlomiej Dragowski!
Mykhaylo Mudryk goal vs. Panathinaikos (49th min, Panathinaikos 0-2 Chelsea)
Mudryk gets on the scoresheet! Neto accelerates down the right flank and floats a lovely ball to the back post, and Mudryk heads into the ground before it bounces into the roof of the net. What an assist by Neto!
Joao Felix goal vs. Panathinaikos (55th min, Panathinaikos 0-3 Chelsea)
It's that same duo again! Mudryk collects the ball on the left inside the penalty area and passes to Felix, who picks up the ball just outside of the box and his central strike deflects past the goalkeeper. That's surely all three points?
Christopher Nkunku goal vs. Panathinaikos (59th min, Panathinaikos 0-4 Chelsea)
Was there any doubt? Christopher Nkunku steps up to take a penalty and sweeps the ball into the bottom-left corner after the the ball struck Daniel Mancini's arm. Chelsea are running riot!
69th min: Panathinaikos 1-4 Chelsea (Facundo Pellistri)
Tete carries the ball forward from a central area in front of Chelsea's penalty area and passes to an overlapping George Vagiannidis on the right before he fires a low cross into the box towards Facundo Pellistri, who manages to pull one back when he tapped home at the back post.
A consolation at least!
MAN OF THE MATCH - MYKHAYLO MUDRYK
Mykhaylo Mudryk has often been overlooked by managers at Chelsea, and while he may not yet be in Maresca's preferred XI, he certainly showcased his talent on Thursday.
The winger set up Felix for the opening goal of the game, scored the winner and registered an assist for Felix's second goal.
Mudryk was also excellent as an outlet for Chelsea to play into, utilising his frightening speed in short bursts and regularly threatened the Panathinaikos backline.
PANATHINAIKOS VS. CHELSEA MATCH STATS
Possession: Panathinaikos 40%-60% Chelsea
Shots: Panathinaikos 8-14 Chelsea
Shots on target: Panathinaikos 3-9 Chelsea
Corners: Panathinaikos 5-6 Chelsea
Fouls: Panathinaikos 8-17 Chelsea
BEST STATS
WHAT NEXT?
Chelsea will host Newcastle United on Sunday in the Premier League at Stamford Bridge, before playing Eddie Howe's side again on the following Wednesday in the EFL Cup.
Meanwhile, Panathinaikos are set to welcome Greek Superleague leaders Aris Thessaloniki FC on Sunday, when they will look to close the gap between the team's to just two points.