The Swiss, who scored six second-half goals, have 18 points from their nine matches and are five points clear of third-placed Slovenia, whose own faint hopes of automatic qualification were dashed in a 1-1 draw at home to Lithuania.
Switzerland, who will finish behind group winners England, play their final match of the campaign in Estonia on Monday.
Slovenia, who conceded an 79th-minute equaliser against Lithuania in Ljubljana, can now only qualify via the playoffs.
The Swiss were initially made to work harder than they might have expected against San Marino after taking the lead when Michael Lang volleyed past Aldo Simoncini from close range after 17 minutes.
They had to wait until 10 minutes into the second half to extend their advantage, however, when Gokhan Inler fired home from the penalty spot following a handball by Davide Cesarini.
Admir Mehmedi steered into an empty net when Simoncini diverted a Fabian Schaer shot into the forward’s path to make it 3-0 in the 65th.
Johan Djourou added a fourth from another penalty on 72 minutes after Schaer was brought down inside the box, before Pajtim Kasami made it 5-0 on 75 minutes with a powerful finish from just inside the box following a cut back from Francois Moubandje.
Breel Embolo converted the third penalty of the night to further extend the lead five minutes later and substitute Eren Derdiyok completed the emphatic win on 89 minutes when Simoncini failed to deal with his close-range header.
(Reporting by Ed Dove and Toby Davis; editing by Ken Ferris)
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