It was a game that both sides knew they needed to win to give themselves a good chance of avoiding the drop, given that Forest's remaining fixtures are tough, travelling to Stamford Bridge and hosting Arsenal, while the Saints commenced proceedings six points from safety.
The stakes were raised even higher with the news of Everton's shock 5-1 victory at Brighton & Hove Albion earlier today, which meant the Tricky Trees were in the relegation zone prior to kick off, with the Saints bottom of the table.
Steve Cooper set his side up to counter attack, and after withstanding some pressure in the opening minutes of the game, with Che Adams spurning a fantastic opportunity, the hosts' game plan was executed to perfection, scoring from their first real chance of the game.
Danilo picked out Brennan Johnson on the right with a fantastic cross-field ball, with the winger squaring to Taiwo Awoniyi, who fired past Alex McCarthy to score his first goal since scoring the winner at St Mary's at the beginning of January.
Having gone seven games without a goal, in the blink of an eye Awoniyi had his second, with Danilo again instrumental in the build-up, picking out the Nigerian just outside the six-yard box, and he made no mistake firing the ball home on the volley.
At two goals to the good, Forest looked like they were cruising, but the visitors refused to go down without a fight, and they made the most of a counter-attack of their own, with Stuart Armstrong squaring to an unmarked Carlos Alcaraz to half the deficit.
Alcaraz's fourth goal of the season offered the Saints a route back into the game, and they did have spells in the first half where they were on top, but their defensive issues were on display again just before half-time.
Ainsley Maitland-Niles clumsily brought down Johnson inside the area, and Morgan Gibbs-White fired the resulting penalty down the middle to restore his side's two-goal lead.
Although it was not mathematically confirmed, Ruben Selles' side knew they were staring down the barrel of relegation at half-time, and they came out fighting early in the second half, with Lyanco nodding home from James Ward Prowse's corner.
The centre-back was again involved in the attacking phase just minutes later, connecting with the ball in the six-yard box, however Keylor Navas made a magnificent save to preserve the Tricky Trees' lead.
Despite some serious pressure from the Saints, Forest were the team that managed to find the all-important sixth goal of the game, with Danilo getting his reward for a fantastic performance, after a clever lay-off from Gibbs-White inside the penalty area.
Nottingham Forest thought they had extended their lead when Felipe slotted home in stoppage time, but VAR confirmed the defender was offside, and Ward-Prowse scored from the penalty spot minutes later, after Romeo Lavia was brought down in the area.
That late goal made it a nervy finish at the City Ground, but the Reds held on to move up to 16th in the Premier League table, now three points clear of the bottom three.
Southampton, on the other hand, are almost certain to be relegated, sitting eight points behind 17th-placed Everton with three games left to play.