An improved second-half performance was not enough to prevent Yeovil from tumbling to their sixth consecutive defeat in a game overshadowed by injury.
Visiting Portsmouth took a deserved lead into the break in League One before Lewis Young was taken off on a stretcher only minutes after coming on.
Reuben Reid’s penalty gave the hosts hope, but Gabor Gyepes pounced on poor defending to seal the points.
Yeovil manager Gary Johnson again rang the changes, recalling four players and switching to a 3-5-2 shape.
Richard Hinds came in for Luke Ayling, operating at the heart of defence as Jamie McAllister and Joe Edwards assumed wing-back roles.
Keanu Marsh-Brown replaced the suspended Ed Upson in midfield, while Gavin Williams and Gozie Ugwu made way for strike duo Reid and James Hayter.
With just five minutes on the clock, Hayter nipped in to claim possession following Adam Webster’s mistake, laying off for Marsh-Brown who burst into the box and drove across goal.
A minute later, Byron Webster’s slip at the other end allowed Izale McLeod a sight of goal, but he too missed the target.
On 11 minutes, McLeod cut inside from the left and shot from the edge of the box. Marek Stech pushed the ball onto the post and gathered as it rebound into his arms.
However, the giant Czech stopper was beaten after 13 minutes. McLeod made the most of a sleepy Yeovil defence to latch on to a ball over the top, smashing home first time.
Reid found himself clean through when Mustapha Dumbuya allowed the ball to drop in midfield on 20 minutes, but could only fire at goalkeeper Mikkel Andersen.
McLeod slid a pass through to Wes Thomas on 32 minutes and, as Hinds attempted the wrestle possession from the AFC Bournemouth loanee, he thumped wide when he should have scored.
Three minutes before the break, Marsh-Brown burst into the box, catching Thomas flat-footed. The Yeovil attacker tangled with his opponent and went to ground, but Chris Foy failed to point to the spot.
The hosts reverted to a 4-4-2 formation after the break, Young and Gozie Ugwu entering the fray in place of Hinds and Hayter.
However, Young spent less than six minutes on the pitch, suffering a serious leg injury that saw him taken off on a stretcher.
With the Glovers improving, Portsmouth enjoyed a chance of their own on the hour mark. Jonny Ertl found space to cross from the right and after the ball worked its way to Jon Harley overlapping, the full-back lashed wide.
Eight minutes later, the hosts levelled. Marsh-Brown’s cross was inches beyond Ugwu and Nathan Ralph, but as Young’s replacement regained possession he was tripped by Dumbuya. Reid stepped up to stroke home the penalty.
Stech could only parry Brian Howard’s long range effort on 72 minutes, but did better from Thomas’ follow up.
Yeovil’s Webster picked up his fifth booking of the season after 77 minutes and seconds later Pompey led again.
Yeovil let a corner bounce in the box and Gyepes turned to lash home.
The Glovers’ fortunes continued to worsen with six minutes of normal time remaining when Reading loanee Ugwu limped off, meaning the Huish Park outfit finished their second game running with ten men.
Yeovil: Stech; Webster, Hinds (Ugwu 46), Burn; Edwards, Blizzard, Marsh-Brown, Smith, McAllister; Reid, Hayter (Young 46, Ralph, 52). Not used: Ayling, Williams, Stewart, Foley.
Goals: Reid pen 68.
Bookings: McAllister (foul), Webster (foul), Burn (foul).
Portsmouth: Andersen; A Webster, Gyepes, Michalik, Harley; Dumbuya, Ertl, Howard, Williamson; McLeod (Obita 88), Thomas (Harris, 82). Not used: Eastwood, Buzsaky, Walker, Compton.
Goals: McLeod 13, Gyepes 78.
Referee: Chris Foy (Lancashire).