The modest south-coast club had thumped Villarreal 5-0 at home in the first leg but were rarely troubled at the Madrigal, taking the lead with a classy backheel from Jorge Molina just after the break.
Guillermo Franco levelled for the hosts soon after but the visitors could even afford to miss a late penalty as both sides finished with 10 men.
Poli Ejido's exploits matched those of another third tier side Real Union who knocked out league champions Real Madrid on the away goals rule on Tuesday, after drawing 6-6 on aggregate.
Barcelona were never comfortable against third-tier Benidorm at the Nou Camp until Lionel Messi scored on the rebound from a penalty near the end, to seal their passage 2-0 on aggregate.
Orihuela were similarly stubborn at the Calderon, holding Atletico Madrid to a goalless draw, though Javier Aguirre's side progressed courtesy of Diego Forlan's first-leg strike.
Cup holders Valencia won 7-1 on aggregate against fourth-tier Portugalete.
Athletic Bilbao , Real Mallorca and Sporting Gijon won through in the all-top flight ties, while 2006 winners Espanyol , Valladolid , Deportivo Coruna , Almeria , Real Betis and Racing Santander all beat off second-division opposition.
The last two ties will be resolved on Thursday when 2007 winners Sevilla host Segunda B side Ponferradina trailing 1-0, and Osasuna receive Getafe with the score at 0-0.