The Seville-based club, who have spent the last two years in the second division, are the only side with a 100 per cent record this season and have a two-point lead over Valencia after four matches.
Malaga are three points off the pace in third spot, one point ahead of champions Barcelona, Sevilla and Levante.
Santa Cruz, on loan from Manchester City, notched his first goal for Betis from close range after seven minutes before Salva Sevilla doubled the lead from the penalty spot.
Zaragoza defender Efrain Juarez pulled one back after Casto made a hash of a cross in the 36th minute.
The game looked to be all but settled after Benat netted a second Betis penalty and Santa Cruz headed their fourth goal on 49 minutes.
Casto's red card then threw Zaragoza a lifeline. The Betis keeper needlessly raced out of his area to bring down Luis Garcia after 69 minutes and Juan Carlos rattled the home side when he volleyed in nine minutes later.
From an identical position Juan Carlos volleyed his second goal, and Zaragoza's third, with 11 minutes to go but the visitors were unable to find the equaliser in a frantic finale.