Little over two minutes had elapsed when Marc Roca should have put the hosts ahead, but he dragged into the side netting after being left in space just yards out.
Some calamitous defending at the other end was then nearly punished when Andre Silva headed against the bar, but it was largely the Spanish side who were on top.
Antony teed up Angel Ortiz for a thumping strike that forced a strong stop out of Diogo Costa, before Abde Ezzalzouli wasted a pair of openings.
Nelson Deossa was the next to take a punt and came agonisingly close to the opener with a 20-yard thunderbolt that whistled past the post, while Roca had a somewhat tamer strike comfortably saved.
That lack of potency left the door open for a suckerpunch that the visitors thought they had delivered when Martim Fernandes unleashed a left-footed rocket that cannoned in off the bar, but it was controversially ruled out for handball after VAR intervention.
Manuel Pellegrini’s side - chasing just a second home win in this competition - might have been frustrated at their failure to score before the break, but finally broke the deadlock shortly after half-time.
Ezzalzouli got it, converting with a peach of a finish as he deliciously curled into the far top corner with his right foot from the left-hand side of the area.
That seemed to wake Porto up, and they equalised before the hour mark with their first shot on target, albeit Alvaro Valles would have been disappointed that he let Gabri Veiga’s 25-yard free-kick burst through his hands.
The second was just as clinical, as Samu made it 2-1 just moments after coming off the bench with a fierce 16-yard strike that rifled past the goalkeeper.
The 2004 UCL winners were well in the ascendancy by now, and had further chances through Alan Varela and Veiga.
Betis made some changes of their own though, and that flipped the game on its head once more.
Cucho Hernandez came off the bench and slotted home after receiving Antony’s pass.
From there, Betis seized the momentum and profited from a soft penalty, given after VAR intervention for a trip by Francisco Moura on Ortiz.
Captain Isco took it, sending Costa the wrong way as he calmly slotted into the bottom left.
The result gives the Spaniards a full complement of six points after two games and extends their unbeaten run across all competitions to seven matches (W6, D1), whereas Porto - who were denied an equaliser when Santiago Gimenez forced a flying, fingertip save out of Valles deep into added time - have lost their opening two matches.
Flashscore Man of the Match: Abde Ezzalzouli (Real Betis)