Betis stormed into an early 2-0 lead thanks to efforts from Benat Etxebarria and Nacho and, although Athletic pulled a goal back through Oscar De Marcos, Salva Sevilla's penalty on the stoke of half-time restored the away side's two-goal advantage.
Both sides had chances to net at the start of the second period before Athletic got a lifeline when Betis defender Mario was sent off in the 75th minute.
Athletic then pulled another goal back through David Lopez's 87th-minute penalty to set up a grandstand finish, but the hosts could not force an equaliser and were also reduced to 10 men in stoppage time when Fernando Amorebieta was dismissed.
Betis join Valencia at the top of La Liga as the only sides still boasting 100% records, while Athletic have just the one point from their three games.
Segunda Division champions Betis started the season with late victories over Granada and Real Mallorca - Ruben Castro netting the winning goal inside the final four minutes of both games - but the Andalusian outfit looked keen to finish Sunday's game off early.
Benat opened the scoring in the sixth minute with a brilliant free-kick from the edge of the box and Nacho doubled the lead in the 13th minute after breaking in from the left touchline and combining with Jonathan Pereira.
Betis came within a whisker of going 3-0 ahead in the 32nd minute when Roque Santa Cruz curled a shot against the far post.
Shellshocked Athletic were in danger of being sunk before half-time but they hit back in the 37th minute when De Marcos bundled the ball home at the second attempt after Espinosa Casto had blocked his first effort.
However, Betis were soon back on the attack and Pereira showed great pace to get in behind the home defence and it needed a good block from Gorka Iraizoz to deny him.
Betis would be celebrating a third goal soon enough though, with De Marcos penalised for handling the ball in the area and Salva slamming the resulting penalty down the centre of the goal.
Athletic tried to stage a recovery at the start of the second half and Javi Martinez and Iker Muniain were both denied by Casto.
De Marcos, Fernando Llorente and Ander Iturraspe also tried their luck but Betis were still threatening going forward and Jefferson Montero should have done better in the 58th minute with only Iraizoz to beat.
Betis then struck the woodwork again in the 60th minute through Pereira.
The visitors suffered a setback when Mario was shown a second yellow card following a fracas with Muniain and that gave Athletic a glimmer of hope.
Soon after Mario's departure Spain international Llorente saw his close-range header magnificently saved one-handed by Casto.
Markel Susaeta also tested Casto before Athletic made it 3-2, Lopez drilling home from the spot following another handball in the area, this time from Francisco Chica.
Athletic pushed for a late equaliser and Lopez volleyed inches wide, but there was no late recovery and the Basque outfit saw Amorebieta receive his marching orders after picking up a late yellow.