Portuguese midfielder Zeca scored twice, while Argentina forward Luciano Figueroa also struck a superb long range strike to seal the win for Giannis Vonortas' team at the neutral Nea Smyrni Stadium.
The tiebreaker, which was required after both teams ended the regular season with the same points and goal difference, almost did not go ahead after Panionios fans, who play their home matches at the ground, broke into the stadium 24 hours earlier damaging the pitch with paint and sprinkling it with nails.
The damage was repaired and the pitch was cleared after an inspection earlier on Thursday.
While there was no European place at stake, Panathinaikos were determined to end their season on a high and the Greens were ahead after 28 minutes when Zeca played a neat one-two with Kostas Barbarousis before finishing clinically.
He made it 2-0 with a deflected shot in the 61st minute after Serge Die had been red-carded for Xanthi for kicking the ball off a prostrate Zeca in frustration, while Figueroa rounded off a comfortable victory with a swerving left-footed strike from the edge of the penalty area.
The Super League playoffs, a mini-league between the clubs who finished from second to fifth in the table which determine Greece's second Champions League spot and Europa League places, begin on May 15.
PAOK Salonika will start with four points as the team who finished second in the regular season, while Asteras Tripolis begin with two points as the third placed-team.
Atromitos and Giannina, who finished fourth and fifth respectively, will start with zero points.