Southampton all but secured promotion to the Championship after confirming Plymouth's relegation with a 3-1 win.
Nigel Adkins' side are now three points clear of third-placed Huddersfield with a far superior goal difference than the Terriers with one match remaining.
Southampton's top scorer Rickie Lambert took his league tally to 21 goals with two strikes as Argyle's south coast rivals tore into Peter Reid's injury ravaged Pilgrims.
Saints took the lead in the 45th minute when Danny Butterfield's deep cross from the right wing was headed home at the far post by Lambert.
The Saints doubled their advantage in the 49th minute when former Argyle defender Ryan Dickson sidefooted in off the post.
Dickson converted a cross by Adam Lallana just seconds after a goalmouth scramble when Radhi Jaidi met a corner with a powerful header that came back off the upright.
Lambert doubled his tally with a coolly executed 59th-minute penalty after being floored on his way to goal by teenage Argyle defender Curtis Nelson.
Saints striker David Connolly crashed a 30 yard strike off the underside of the bar in the 85th minute.
In stoppage time Yannick Bolasie sidefooted home Argyle's consolation goal from 15 yards.
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