Orejuela, 34, scored twice in the space of 11 minutes to give Inti Gas a three-goal buffer at half-time after team-mate Fernando Oliveira opened the scoring.
San Simon pulled two goals back early in the second half but Inti Gas held on for back-to-back wins.
Inti Gas have collected 21 points from 10 games and are one point clear of undefeated Melgar, who were 2-1 winners over Universidad San Martin.
San Simon are on a four-game losing streak, conceding 13 goals in that period to sit second-bottom in the standings.
Inti Gas made the perfect start at the Estadio Ciudad de Cumana, when Oliveira was on hand to head home from inside the six-yard box in the 18th minute after San Simon goalkeeper Federico Nicosia was caught off his line.
It got better for the hosts in the 34th minute following the referee's decision to award a penalty for handball and Orejuela made no mistake, sending the keeper the wrong way.
Orejuela was in the thick of the action on the stroke of half-time, side-footing from close range after some brilliant play out wide.
San Simon emerged from the break with renewed optimism and it resulted in quick-fire goals through Jesus Rey and Carlos Zegarra but they could not find the equaliser as Inti Gas claimed maximum points.
Melgar are within striking distance of Inti Gas after Thursday's hard-fought 2-1 victory at home to Universidad San Martin.
Alejandro Hohberg made the breakthrough in the 36th minute only for Universidad San Martin's Santiago Silva to level proceedings on the hour-mark at the Estadio de la Universidad Nacional San Agustin.
However, Melgar consolidated second spot and preserved their unbeaten start to the season after Bernardo Cuesta struck with seven minutes remaining.
In other results, Cienciano rose to third in the table thanks to a 2-1 triumph over Alianza Lima and some favourable results elsewhere.
Juan Aurich (17 points, +8) lost 3-1 to UTC Cajamarca, while Cesar Vallejo (17 points, +6) were beaten 1-0 at Los Caimanes, paving the way for Cienciano (18 points, +5).
Seventh-placed Sporting Cristal routed Leon de Huanuco 4-0 in a comprehensive display.
Mario Velarde scored twice as Union Comercio accounted for Sport Huancayo 3-0 and Universitario downed Real Garcilaso 2-1.