Miguel Michu opened the scoring for the hosts before Raul Tamudo made it two six minutes into the second period, and although Julien Escude pulled one back for the visitors just after the hour, Rayo held on for their first win in five in La Liga.
Sevilla, meanwhile, have now lost three on the spin in the league and are losing ground on their rivals in the race to land a Champions League berth.
Sevilla coach Marcelino Garcia Toral wasted no time in selecting Reyes in his starting line-up after his arrival from Atletico Madrid earlier this week for a reported fee of 3.5million euros.
Reyes began his career with Sevilla over a decade ago prior to a big-money move to Arsenal, but his return after nearly eight years away was not graced with any clear-cut chances in front of goal as the Rayo backline turned in a disciplined performance.
Reyes' only effort of note in the opening 45 minutes came with a hopeful 30-yarder that was always rising too high, while Antonio Luna's shot wide of the left upright was the only other chance for the visitors in a listless opening period.
The hosts were also reduced to optimistic efforts by Roberto Trashorras and Tamudo before they made the breakthrough on the stroke of half-time when Trashorras' free-kick was not effectively dealt with by Sevilla goalkeeper Javi Varas and Michu had a simple task to head home.
The lead was doubled after 51 minutes when Piti centred the ball from the left wing and the experienced Tamudo created space on the edge of the area before firing home.
Sevilla clawed their way back into the match 10 minutes later when Escude lashed home on the rebound after Ivan Rakitic's shot was not held by Dani Gimenez.
Dani redeemed himself after 66 minutes, however, saving smartly from Alvaro Negredo's close-range effort.
Reyes' second Sevilla debut came to an end after 77 minutes as Garcia Toral threw on Piotr Trochowski in a bid to force the equaliser, but Rayo remained steadfast to secure their first league win since November 6.