Having scraped a 1-0 victory seven days ago, Panathinaikos began the night in pole position to progress.
But that changed just seven minutes in, when a speculative long-range shot from Cucho Hernandez cannoned off the bar and into the path of makeshift striker Ruibal, who calmly chested the ball down and rifled in to level the tie.
Panathinaikos couldn’t get into the game, and the Verdiblancos should have added another three minutes later, as only a perfectly-timed tackle from Sverrir Ingi Ingason stopped Pablo Fornals from converting at the near post after he found space inside the box.
Andrews Tetteh was a lone bright spark for the visitors, but he was guilty of squandering a promising opportunity when firing straight at Pau Lopez just after the half-hour mark - something that would be punished severely on the stroke of half-time, when Sofyan Amrabat put Betis ahead in the tie.
Thinking he was offside when exchanging passes with Ricardo Rodriguez, the Moroccan petulantly - and inadvertently - skied a ball to his compatriot Abde Ezzalzouli.
He tried to play Rodriguez in, but Renato Sanches’ attempted tackle saw him give possession back to Amrabat, who unleashed a curling exocet into the top-left corner of Alban Lafont’s net.
Having scored more than once for only the second time in six competitive outings, Betis were expected to put Panathinaikos to the sword after half-time.
And within eight minutes of the restart, they were home and dry thanks to Cucho Hernandez timing a run to perfection, where he darted in to receive Marc Bartra’s delicately lofted pass into the area and sidefoot past a helpless Lafont.
Almost inevitably, that was met with a double change from the Panathinaikos bench, but it made no obvious impact on what was quickly turning into a landslide.
In fact, Betis only grew in strength after a double switch of their own, and netted a fourth that illustrated the gulf in class, as Cucho’s pass to Ezzalzouli set him free to burst down the left flank and zero in on goal.
However, rather than try his luck at the near post from an awkward angle, he unselfishly squared back for Antony to side-foot in and cap off a fine team goal.
Only the swift diving of Lafont prevented Marc Roca from netting a fifth with a quarter hour still to play, while the same kind of defiance saw him deny Antony a brace on the night, as the former Manchester United man rushed through one on one.
Though there was no lack of effort in their quest for a five-goal margin of victory - a feat that would have marked their first such win in a main draw European tie since 1998 - Betis ultimately declared at four, with half a mind by now on their looming quarter-final tie with fellow aggregate deficit busters Braga.
April 9th and 16th will be circled in the Verdiblancos’ diaries for that meeting with Portugal’s greatest threat to the Big Three, after a heroic display that made a mockery of Panathinaikos’ now-tattered nine-game unbeaten run.
Flashscore Man of the Match: Cucho Hernandez (Betis)
