The England international struck either side of half-time to secure the victory for Arsene Wenger's men despite Mesut Ozil's missed penalty to keep them top of Group F
Arsenal – who are aiming to qualify for the tournament's knockout stages for the 11th year in a row - were thoroughly dominant at the Emirates Stadium on Tuesday, with Wilshere's goals in the first and 65th minute enough for their fourth Group F win in five attempts despite Mesut Ozil's saved first-half penalty.
Only profligacy and the efforts of Marseille goalkeeper Steve Mandanda kept the scoreline respectable for the visitors, who have lost all five of their group matches.
Qualification to the last 16 – in what was described as the pre-tournament group of death – can be achieved by Arsene Wenger's side if they win a point in their final fixture in Napoli next month.
Unable to reach the next stage, Marseille made six changes, as the likes of Mathieu Valbuena and Florian Thauvin dropped to the bench, while Tomas Rosicky, Mathieu Flamini and Nacho Monreal returned for Arsenal.
Arsenal burst out of the blocks and took just 27 seconds to open the scoring, as Bacary Sagna's pass down the right played in Wilshere, who ran into the area, sidestepped a challenge from Lucas Mendes and curled a left-foot effort into the top corner.
It was a delightful start and Arsenal should have doubled their lead in the sixth minute, but Aaron Ramsey shot straight at the legs of Mandanda when played through by Wilshere, while Andre-Pierre Gignac headed wide at the other end.
The hosts dropped off the pace significantly after Ramsey's effort, with their lull highlighted by a sloppy first touch from Ozil in the penalty area following a delightful lofted ball from Ramsey.
Arsenal goalkeeper Wojciech Szczesny was quick off his line to deny Gignac as he tried to round him, and eight minutes before the break, Wenger's men won a penalty when Ramsey was brought down by Nicolas N'Koulou after an excellent flick.
The initial contact appeared to be outside the area and Ozil failed to convert from the spot, stuttering before hitting a low left-foot effort that was comfortably beaten away by Mandanda.
Arsenal ramped up the pressure after the break, with Olivier Giroud shooting straight at Mandanda before the same player had an effort nearly creep in following a Kassim Abdallah deflection.
Ozil was next to test Mandanda with a stabbed effort, but they finally extended their advantage when the German's neat ball from the right was steered in by Wilshere from close range.
Thauvin had three chances for the visitors in the space of six minutes, one of which was cleared off the line by Monreal with 16 minutes left, while another forced a top near-post save from Szczesny, but it was too little too late for the French outfit.
Substitutes Santi Cazorla and Theo Walcott also missed late chances at the other end, but two goals were enough for Arsenal.