An own goal from Sevilla defender Federico Fazio midway through the second half put Athletic ahead and the hosts settled the contest with Andoni Iraola`s late penalty.
The triumph sees Athletic climb up two places to fifth in the Primera Division standings, taking advantage of Espanyol`s shock defeat to Levante earlier this evening.
Sevilla, who had gained seven points on Athletic in their previous three games, are now two points behind Espanyol and the Europa League places.
The Andalusian club`s plight at San Mames was not helped by injuries to their two starting forwards Alvaro Negredo and Luis Fabiano.
Negredo was replaced early following a head blow, while Luis Fabiano was stretchered off in the second half with what looked to be a knee injury.
Athletic, who also lost one of their strikers to injury with Gaizka Toquero limping off holding his hamstring right at the start of the second half, were the first to threaten when Spain striker Fernando Llorente brought a flying save out of Javi Varas with a glancing header.
Varas then tipped wide a Javi Martinez header before Ivan Rakitic saw an effort go just wide for Sevilla.
The visitors had another chance at the start of the second half but Frederic Kanoute, who had replaced Negredo in the 15th minute, mis-hit his shot wide after being picked out by Martin Caceres.
The deadlock was broken in the 66th minute when Fazio put through his own goal.
Athletic full-back Koikili drove in a low cross from the left which was missed by two players at the front post and Fazio, in attempting to clear the ball for corner, succeeded only in drilling a low shot past Varas at his near post.
That was a big blow for Sevilla, and it was to get worse moments later as, after Varas had prevented Oscar De Marcos making it 2-0, the visitors lost Brazil ace Luis Fabiano to injury.
Sevilla tried to mount a fightback from those setbacks and Kanoute was denied twice in quick succession by Athletic goalkeeper Gorka Iraizoz.
However, their hopes of snatching a point were crushed when Athletic doubled their lead from the penalty spot in the 89th minute.
An Athletic corner was picked up by Sevilla defender Julien Escude but, after taking a touch, he was beaten to the ball by De Marcos and ended up bringing down the home substitute as he attempted a sliding clearance.
Iraola, wearing a bandage following his early clash of heads with Negredo, stepped up to smash the resulting penalty past Varas to not only secure Athletic the victory but also guarantee them the better head-to-head record against Sevilla having lost 4-3 away from home.