John Sheridan returned to haunt Chesterfield and leave his former employers’ aspirations of reaching the League Two play-offs hanging by a thread.
A wonder-strike from Joe Bryan put Plymouth ahead before Curtis Nelson doubled the visitors’ lead moments later.
An own goal from Guy Branston gave the Spireites hope midway through the second half but Paul Cook’s side were unable to use it as a springboard to set up a tense finale.
Chesterfield remain four points adrift of seventh-placed Bradford City, who lost 2-0 at home to Rotherham.
Cook made just one change to the side who drew at home with Bradford City, with Marc Richards coming back into the side in place of Armand Gnanduillet.
In unaccustomed fashion, Chesterfield attacked the Karen Child Stand first half.
Tommy Lee was forced into a crucial block early on to deny Conor Hourihane from giving the visitors the lead after Reuben Reid’s knock down had sent Argyle’s skipper through one-on-one.
The striker then blasted over from a promising position on the edge of the area before the Spireites threatened for the first time.
Drew Talbot’s deep cross to the far post was met by Tendayi Darikwa, who’s tame header was easily picked up by Jake Cole.
Darikwa and O’Shea combined well before the Irishman fired a ball across the six yard box that just escaped the attention of Richards.
It was all too easy for Argyle and the visitors took advantage on 20 minutes with the game’s opening goal.
A well worked move saw the ball shifted wide to Bryan, who checked in on his right foot and curled a wonderful strike around Lee’s dive and into the far corner of the net.
Chesterfield were visibly rocked and they fell further behind minutes later when Nelson latched on to Reid’s header to poke the ball over Lee from within the six yard box.
The Spireites were at sixes and sevens before a simple move through the heart of Argyle’s team almost gave them a foothold.
Liam Cooper passed short to Mark Randall, who found O’Shea, who released Richards. The striker’s cross sailed just over the head of Drew Talbot but it was a passage of play that restored some hope in the home faithful.
Cooper was then inches away with a diving header from connecting with Conor Townsend’s inviting in-swinging corner.
It proved to be a brief respite for the hosts, who had Neal Trotman to thank for reading the run of Reid as he threatened to split the centre-halves just before the break.
Townsend forced a corner after he skipped past Durrell Berry in the opening exchanges of the second half and crossed for Richards, whose shot was blocked. Cooper rose at the back post but headed over from the left back’s resulting corner.
And the centre-half was given a huge let-off when his short back pass was pounced on by Bryan, but the winger put his shot wide as he attempted to round Lee from the angle.
A double substitution saw Alex Henshall and Gnanduillet introduced in place of Richard Brindley and Richards.
And it paid immediate dividends when Henshall’s powerful cross was inadvertently turned into his own net by Branston from five yards - with no blue shirt in sight.
The on loan winger from Manchester City tormented the opposition defence at every opportunity and produced a handful of telling centres.
There was almost controversy when Randall’s pass was blocked by referee Nigel Miller and fell to the feet of substitute Nick Chadwick. The striker turned and slotted the ball to the left of Cooper for the onrushing Andres Gurrieri who, with the goal at his mercy, fired wide of Lee’s top right hand corner.
Talbot fired one well over Cole’s crossbar as the game came to an end, much-like Chesterfield’s aspirations of promotion.
Spireites: Lee; Brindley (Henshall 54), Cooper, Trotman (Hird 72), Townsend; Darikwa, Talbot, Randall, Togwell; O’Shea; Richards (Gnanduillet 54)
Subs not used: Barrington, Clay, Boden, Wafula
Argyle: Cole; Berry, Wotton, Branston, Bhasera, Cowan-Hall, Nelson, Hourihane (c), Bryan, Reid (Chadwick 80), Guerrieri
Subs not used: Gilmartin, Charles, Blanchard, Young, Murray, Harvey
Bookings: Talbot 35, Randall 63; Berry 41
Referee: Nigel Miller