Two second-half strikes – a Leonardo Pavoletti header and a Joao Pedro penalty – sealed a monumental win for the Sardinians, pulling them just two points behind Torino in 17th place, despite having Charalampos Lykogiannis sent off towards the end of the game.
Semplici took over and immediately changed to a 3-5-2 formation in the hope of reversing Gli Isolani’s woeful run, with Pavoletti preferred to Giovanni Simeone as strike partner for captain Joao Pedro.
Giovanni Stroppa was forced into making his first change on 20 minutes with Niccolo Zanellato replacing the injured Milos Vulic, and moments later his team broke away with Alessio Cragno having to react smartly to keep out a goal-bound deflection from teammate Alfred Duncan.
A couple of marauding Diego Godin runs from deep were the best that Cagliari had to offer as both sides continued to fight for every ball, with the game really feeling like a relegation six-pointer the longer the half went on.
The Calabrians were then forced into their second change of the game on 39 minutes, Eduardo Henrique coming on in place of Salvatore Molina, who worryingly left the pitch on a stretcher. A few more tough comings-together happened before the sides went in goalless.
Both sides started the second half as they had the first, and Cagliari had to make more fouls to control their hosts. Substitute Henrique saw his header cleared off the line by Godin in what was the best chance of the game on the 52nd minute as the Pitagorici began to turn the screw.
Then came the opener, Pavoletti rose fantastically to nod in a deep Lykogiannis cross at the back post on the 56th minute as Gli Isolani found the net for only the second time in seven games, fully justifying his selection.
The away side broke again after the restart, Nahitan Nandez seeing his shot saved before Pavolotti was upended in the box to win Casteddu a penalty, Lisandro Magallan booked for his efforts.
Up stepped Joao Pedro to hammer an unstoppable drive into the top left-hand corner to give his side a 2-0 lead, just four minutes after taking the lead, for his 12th goal of the season.
Ounas came close to haunting his ex-teammates but his lovely, curling effort from the edge of the box came back off Cragno’s upright with the keeper left rooted to the spot.
Lykogiannis was given his second yellow and therefore his marching orders on the 75th minute to leave his side with ten men for the remainder of the game.
Pedro Pereira curled a 90th-minute freekick towards the top corner, a shot that looked destined for the back of the net, before Cragno pulled off one of the saves of the season to keep a clean sheet and to seal a potentially season-saving victory for Casteddu.