Three goals in the opening 30 minutes put the game beyond Pompey, before Marlon Pack's own goal assured Derby of three points that moved them away from the relegation zone.
The hosts took just eight minutes to break the deadlock, splitting Portsmouth open with two impressive throughballs before Nathaniel Mendez-Laing squared it into the box to set up Kane Wilson's close-range finish.
Eiran Cashin rose high to thump a powerful header in for their second, with Ebou Adams adding to their tally just before the half-hour mark with the help of a big deflection off Tom McIntyre.
Jerry Yates forced a good save out of Nicolas Schmid before the break, though Derby took their foot off the gas in the second half before Marcus Harness, formerly of Portsmouth, saw his low cross turned in by Pack in the 65th minute.
They could have made it five late on - Abdoulaye Kamara's blind backpass was almost pounced on by Kayden Jackson, who had wrongfooted the goalkeeper, but Schmid scrambled back to his line to spare the defender's blushes.
Data Debrief: Total dominance
From that performance, it is hard to believe Derby had not won a match in the Championship since early November, but they did not look back after a stellar first half.
The Rams scored with their first three shots on target, having seven overall from their 17 efforts as they created 1.14 expected goals (xG).
Portsmouth, meanwhile, remain just above the drop zone, only above Cardiff City having scored more goals. However, they failed to test Jacob Widell Zetterstrom once on Friday, despite having one big chance.
The 53-year-Hislop, who made 53 appearances for Newcastle United from 1995-1998, currently works as a football pundit on ESPN FC. During his time at Newcastle, Hislop used his influence to combat discrimination after an incident in which he was racially abused by a group of youngsters at a petrol station opposite the club’s ground, St James' Park.
In 1996, he was instrumental in the founding of Show Racism the Red Card. That work continues today.
He shared on Instagram his gratitude for being recognised.
“Fifty-five years ago, Newcastle University bestowed Dr Martin Luther King with an Honorary Doctorate in Civil Law. Dr King’s speech was a call for racial equality, a sharing of those responsibilities regardless of where you call home,” he said.
“Dr King’s and NU’s legacies continue to shape the civil rights responses of today.
I am humbled that Newcastle University deemed me worthy to receive an Honorary Doctorate as well. I accept in recognition of the thousands who have supported, contributed, volunteered and worked for Show Racism the Red Card.
“I accept in recognition of all who remain undaunted by the task, who give of themselves knowing they may never savour an equal world themselves.”
In closing, he thanked Newcastle University Chancellor Imtiaz Dharker, Vice Chancellor and University President Chris Day as well as Show Racism the Red Card founder Ged Grebby as well as Matin Cox, who nominated him for the award.
He also expressed gratitude to his wife Desha Hislop and his children.
A goalkeeper in his playing days, Hislop made 26 appearances for Trinidad and Tobago between 1999 and 2006. During his club career, he was also the man between the sticks for Reading, West Ham and Portsmouth in England before playing for FC Dallas during the 2006/2007 season.
Pompey looked to be missing their opportunity in front of their own fans when, needing one point to return to the second tier after a 12-year absence, they were 2-1 behind after Devante Cole and John McAtee struck either side of Kusini Yengi’s equaliser.
But the hosts hit back in the final seven minutes with Colby Bishop scoring from the penalty spot and Conor Shaughnessy heading home the winner.
Mousinho told BBC Radio Solent Sport: “I think once everything settles down it will sink in properly. I’ve never experienced anything like that, the last 15 minutes, it was absolutely incredible.
“Even at 2-1 down, to get the momentum and the crowd behind us, I am just so proud of the boys. I’m genuinely just so pleased for everyone connected to the football club. They’ve gone through so much.
“When we got it back to 3-2 I thought we have played so poor, but found a way to win somehow in a game where we really struggled. It really does sum up the boys.
“A tough night, tough conditions, but they got the job done. It’s hard for me to sum it up, but I get what’s happened over the last 15 years at the club and how difficult it was, on the brink of liquidation, to come back and have a night like this is incredible to be involved in.
“To be head coach, it is a privilege. Hopefully we can have a few more nights like this.
“I never could have imagined this happening this quickly. This was obviously the goal at some point, but didn’t think it would happen with two games to go this season. It is a remarkable achievement. That is a serious effort to be crowned champions ahead of some of the big boys in this league as well.”
Play-off chasing Barnsley, having lost three of their last four games, are four points above seventh-placed Lincoln.
Boss Neill Collins told the club’s official website: “There are a lot of positives. But the biggest frustration is that all those positives didn’t add up to what I thought would be a deserved victory.
“We perform like that, we’ll be fine. We’ll win games. It’s just the fine margins. For me, it’s the fine margins that have gone against us the past four or five games.
“Tonight again, it’s some of our doing. But that’s what we need to concentrate on. That’s what the Football League is all about.”
Daniel Farke's side moved to within two points of Sunderland after coasting to a 2-0 victory over Queens Park Rangers at Elland Road.
Jayden Bogle sliced home after 19 minutes for Leeds, who made sure of victory in stoppage time as Joel Piroe came off the bench to score.
There was no such success for Sunderland despite Wilson Isidor and Dennis Cirkin both finding the net in the first half at the Stadium of Light.
Haji Wright pulled one back for Coventry, who dismissed long-term boss Mark Robins this week, just past the hour before Jack Rudoni snatched a 2-2 comeback draw with six minutes remaining.
At the other end of the table, Portsmouth managed just their second victory of the season with a 3-1 triumph over Preston North End at Fratton Park.
Josh Murphy and Connor Ogilvie were both on target in the first half before Colby Bishop's late penalty sealed victory after Emil Riis Jakobsen had reduced the deficit for Paul Heckingbottom's visitors.
Victory moved Portsmouth up to 23rd in the league, two points ahead of bottom side QPR and within three points of safety.
Fellow strugglers Plymouth Argyle also gained a point as Adam Randell's 41st-minute strike cancelled out Jerry Yates' early opener for Derby County at Pride Park.
The 1-1 draw leaves Wayne Rooney's side 16th in the table, but just one point clear of the relegation zone, while Derby sit comfortably 12th.
Norwich City dropped down the table in Saturday's other game, suffering their first home defeat in the league in 22 games after a 2-0 reverse against Bristol City at Carrow Road.
Anis Mehmeti and Nakhi Wells scored in either half for Liam Manning's visitors, who moved into 10th with a victory that left them just two points shy of the play-off positions.
Daniel Farke's side edged a seven-goal thriller with a last-gasp winner against Swansea City on Sunday, but had no such drama to contend with three days later at Elland Road.
Sam Byram scuffed an early chance but inadvertently teed up his own sumptuous volley for a 10th-minute lead, before Joel Piroe scored on the rebound from close range on the stroke of half-time.
Substitute Dan James made sure of a routine win in the second half as Leeds moved ahead of second-placed Sheffield United on goal difference, with that pair two points clear of Burnley.
At the other end of the table, Queens Park Rangers climbed off the bottom spot with a 2-0 away triumph over Cardiff City thanks to Zan Celar's first two goals for the club.
The Slovenia international faced heavy criticism after missing a penalty in Saturday's draw with Stoke City, but silenced his critics with strikes in either half at the Cardiff City Stadium.
Fellow strugglers Portsmouth slipped down to the bottom of the league after their match was postponed against Millwall due to floodlight failure at Fratton Park.
Play-off hopefuls Middlesbrough had scored 15 goals across their three-game winning streak, though that came to an abrupt halt after Dominic Hyam's 83rd-minute strike snatched victory for Blackburn Rovers.
Michael Carrick's side still sit sixth, occupying the last play-off spot, but Blackburn's victory saw them jump up to eighth and just two points behind their hosts at the Riverside.
Swansea City secured a 2-1 victory over Derby County in Wednesday's other game, with the visitors doing the damage in the first half after goals from Zan Vipotnik and Ronald.
Nathaniel Mendez-Laing pulled one back for Paul Warne's hosts at Pride Park, where defeat left Derby 15th and four places behind Swansea, who bounced back from successive defeats previously.
Watford goalkeeper Daniel Bachmann was at fault at Elland Road, inadvertently palming Largie Ramazani's fourth-minute strike in before a similar error led to Brenden Aaronson's goal three minutes later.
Bachmann parried Willy Gnonto's cross into Aaronson's path, with the United States international converting a routine finish for his third league goal of the season.
Kwadwo Baah pulled one back shortly after the interval, though Leeds held on to make it six matches unbeaten and move level on points with league-leading Sunderland, who visit Luton Town on Wednesday.
Further down the table, Norwich City missed the chance to move into the play-off positions after coming from two goals down to draw 2-2 at Preston North End.
Leeds loanee Sam Greenwood scored from the penalty spot before setting up Duane Holmes after 12 minutes, though in-form Borja Sainz reduced the arrears on the stroke of half-time.
Shane Duffy then headed Josh Sargent's cross home in the second half to secure a share of the spoils, leaving Norwich a point behind sixth-placed Blackburn Rovers, who host West Brom in their game in hand.
Stoke City let a similar lead slip in a 2-2 draw with Bristol City, who were inspired by Nahki Wells' quickfire second-half double after falling two goals behind in the first half at bet365 Stadium.
On-loan Liverpool prospect Lewis Koumas needed just two minutes to open the scoring before setting up Andrew Moran, whose side could not hold onto their advantage in a disappointing collapse.
Cardiff City also propelled themselves further away from the relegation zone, following Saturday's 5-0 thrashing of Plymouth Argyle with a 2-0 victory over Portsmouth at home.
Regan Poole's sixth-minute own goal before Callum Robinson scored for the second time in as many games, as Cardiff jumped to 19th with a comfortable victory over the Championship's bottom side.
Watford goalkeeper Daniel Bachmann was at fault at Elland Road, inadvertently palming Largie Ramazani's fourth-minute strike in before a similar error led to Brenden Aaronson's goal three minutes later.
Bachmann parried Willy Gnonto's cross into Aaronson's path, with the United States international converting a routine finish for his third league goal of the season.
Kwadwo Baah pulled one back shortly after the interval, though Leeds held on to make it six matches unbeaten and move level on points with league-leading Sunderland, who visit Luton Town on Wednesday.
Further down the table, Norwich City missed the chance to move into the play-off positions after coming from two goals down to draw 2-2 at Preston North End.
Leeds loanee Sam Greenwood scored from the penalty spot before setting up Duane Holmes after 12 minutes, though in-form Borja Sainz reduced the arrears on the stroke of half-time.
Shane Duffy then headed Josh Sargent's cross home in the second half to secure a share of the spoils, leaving Norwich a point behind sixth-placed Blackburn Rovers, who host West Brom in their game in hand.
Stoke City let a similar lead slip in a 2-2 draw with Bristol City, who were inspired by Nahki Wells' quickfire second-half double after falling two goals behind in the first half at bet365 Stadium.
On-loan Liverpool prospect Lewis Koumas needed just two minutes to open the scoring before setting up Andrew Moran, whose side could not hold onto their advantage in a disappointing collapse.
Cardiff City also propelled themselves further away from the relegation zone, following Saturday's 5-0 thrashing of Plymouth Argyle with a 2-0 victory over Portsmouth at home.
Regan Poole's sixth-minute own goal before Callum Robinson scored for the second time in as many games, as Cardiff jumped to 19th with a comfortable victory over the Championship's bottom side.
While three of the top four were at home on Tuesday, Daniel Farke's side arguably had the toughest assignment.
But Boro were swept aside by Leeds despite the visitors benefiting from a Maximilian Wober own goal that cancelled out Wilfried Gnonto's early opener.
Leeds had to wait until the 74th minute to restore their lead through Daniel James, before Brenden Aaronson's stoppage-time goal made sure of a 3-1 victory.
Elsewhere, Burnley could muster only a goalless draw at home to Derby County, while Sunderland required a last-gasp leveller from Patrick Roberts at home to Bristol City, drawing 1-1.
Although Sheffield United could replace Leeds at the summit on Wednesday, Farke's side are now three points clear of third-placed Burnley and four clear of Sunderland in fourth.
Blackburn Rovers leapfrogged Boro into fifth after beating Sheffield Wednesday.
At the other end of the table, Portsmouth climbed out of the bottom three on goal difference after a 0-0 draw at home to Norwich City, but there was no respite for Wayne Rooney and Plymouth Argyle.
After back-to-back thrashings at Norwich and Bristol City, Plymouth suffered their first home defeat since August, going down 2-1 to Swansea City in a result that leaves them 23rd.
The former Tottenham academy player was 25.
Walkes, who was born in London, had played in MLS since 2020, when he joined Atlanta United after leaving Portsmouth.
He moved to Charlotte for the 2022 season after being selected in the 2021 MLS expansion draft. He made 23 league appearances in his debut season.
Following his shock death, Charlotte paid tribute to the family man.
"Everyone at [the club] is devastated by the tragic passing of Anton Walkes," Owner David Tepper said in a statement. "He was a tremendous son, father, partner and teammate whose joyous approach to life touched everyone he met.
"Anton made those around him better people in all areas of life and represented Charlotte FC to the highest standard both on and off the pitch.
"He will be greatly missed by many and our thoughts and prayers are with Anton's family during this heart-breaking time. The club offers its full support to all those impacted during this period of mourning."
Connor Ogilvie handed Portsmouth a deserved lead a minute before half-time after a corner kick found the defender unmarked at the back post to fire home.
But Wednesday responded strongly after the break, levelling through Josh Windass who finished from close range after Michael Smith's clever knock-down.
Smith then sealed the win in stunning fashion in the 70th minute, rifling a sweet first-time strike from outside the box into the top corner against his former club.
Portsmouth are still without a win at Fratton Park since their return to the Championship, and have now lost 12 points from winning positions in the second tier this season, more than any other team.
"I’m disappointed, especially with the nature of losing after going a goal up into half-time," Mousinho told BBC Radio Solent.
"It was a contrasting performance, from Tuesday night at Cardiff, but ultimately, we haven’t done enough to win the game and weren’t quite good enough to do it.
"I’m still really upset with the fact we lost it, but there was a very different message to the players in the dressing room compared to Tuesday.
"That being said, we still have to be a lot better."
But for Sheffield Wednesday and Danny Rohl, they are now unbeaten in their last three away games, and moved into the top half of the table ahead of this weekend's action.
The Owls face Premier League side Brentford in the last 16 of the EFL Cup next Tuesday, and Rohl believes the comeback win can only be a positive moving forward.
"It was a strong comeback after being 1-0 down," Rohl told BBC Radio Sheffield.
"First half we were okay but we changed things at half-time. Coming from behind at Coventry and now here shows a step forward in our development.
"It's just three points, we climb the table eight places with a win but if you lose you drop down.
"But for me it's more important to improve and there is still room for that."
Borja Sainz scored and provided two assists as the Canaries stretched their unbeaten run to 20 home league games, teeing up strikes by Marcelino Nunez and Josh Sargent within four first-half minutes.
Sargent hit the post with a penalty after Lewis Coyle was penalised for handball, but Kaide Gordon gave them a three-goal lead with a scrappy finish soon afterwards.
Sainz then got in on the act with his eighth league goal of the campaign late on, lobbing Ivor Pandur as Johannes Hoff Thorup's team went sixth in the table, leaving Hull 11th with 12 points.
Elsewhere, Burnley missed the chance to go top of the table as they played out a goalless draw with local rivals Preston North End at Turf Moor.
Scott Parker's side dominated possession but struggled to carve out clear-cut chances against their stubborn visitors, for whom Kaine Kesler-Hayden struck the crossbar with an attempted cross.
A dour second half saw few opportunities at either end, as Burnley stayed below Sunderland and Sheffield United, while Preston climbed to 19th on nine points.
In the last of Saturday's three early kick-offs, Louie Sibley's goal earned Oxford United a 1-1 draw at Portsmouth after Mark O'Mahony opened the scoring just before the hour.
Portsmouth remain the only team in the division without a win, earning five points from nine matches, while Oxford are seven points better off, just inside the top half.
Mowatt struck twice in the second half after Josh Maja had given Carlos Corberan's men an early lead at Fratton Park, as Portsmouth's wait for a first win of the season continued.
Maja needed just 54 seconds to put Albion ahead, slamming home for his fifth goal of the season after Tom Fellows got to the byline to cut it back.
The visitors started the second half almost as quickly as they began the first, doubling their lead on 51 minutes as Mowatt curled home left-footed following fine combination play from John Swift and Karlan Grant.
If Mowatt's first goal was good, his second was outstanding as he capped the result in stoppage time, whipping a free-kick into the top-right corner to give Norris no chance.
West Brom's fourth win of the season sees them move one point clear of Sunderland at the summit, while Portsmouth slip to 23rd, only taking three points since their promotion from League One.
Data Debrief: Maja out on his own
Maja's fifth goal of the season took him one clear at the top of the Championship's scoring charts, ahead of Blackburn Rovers' Yulo Ohashi, Oxford United's Mark Harris and Millwall's Duncan Watmore (all four).
Maja was certainly busy on Sunday, attempting more shots (six) and accumulating more expected goals (1.03 xG) than anyone else on the pitch, while also laying on one chance.
The game started slowly, with the hosts not opening the scoring until a 75th-minute Anis Mehmeti penalty after a foul on Sinclair Armstrong by goalkeeper Michael Cooper.
The Blades showed great character to haul themselves back into the game, with 18-year-old Ryan One scoring the equaliser in the 86th minute.
But things went up a notch in stoppage time when Robert Dickie was given a straight red card for a cynical foul on Callum O'Hare 35 yards out.
The drama wasn't finished yet and with seconds to go, Harrison Burrows smashed home a left-foot rocket to win the game for the Blades.
At the bottom of the table, Plymouth opened a four-point gap between themselves and the relegation zone with a 1-0 victory over bottom-of-the-table Portsmouth.
The victory means that Wayne Rooney's side have dropped just two points in their last five games at Home Park, having lost six on the bounce in all competitions away.
It is now four without a victory for Portsmouth, who have earned just nine points in their opening 14 matches back in the Championship.
Elsewhere, Middlesbrough responded to their 3-0 defeat at home to Coventry City last weekend by beating second-bottom Queens Park Rangers 4-1 on the road.
That was a first victory in three for Michael Carrick's side, who are one place below the play-off positions and trail only by goal difference.
QPR are four points behind fourth-bottom Preston North End, having failed to win any of their last 10 league games.
The Baggies were made to wait until the 62nd minute before opening the scoring through Josh Maja, and it was a goal that came against the run of play.
Plymouth had started the second half better, but were unable to make their chances count before Maja's tap-in ultimately settled it.
The victory is a fifth in six matches and fourth in a row for Carlos Corberan’s side, who reclaimed first place from Sunderland and have opened a three-point gap to third-placed Burnley. Plymouth, meanwhile, are 20th and just one point above the relegation zone.
Elsewhere, Leeds United moved into the top six following a 2-0 win away to 10-man Cardiff City, who are bottom of the table.
Defender Joel Bagan was sent off for the hosts after 23 minutes after he was adjudged to have been the last man after a challenge on Willy Gnonto.
It got even worse for Cardiff seven minutes later as Largie Ramazani scored his first Leeds goal.
Cardiff goalkeeper Jak Alnwick saved Pascal Struijk's second-half penalty, but an effort from former Swansea City striker Joel Piroe on 87 minutes wrapped up the points for Daniel Farke's side. Cardiff boss Erol Bulut, meanwhile, looks under increasing pressure.
Burnley snatched a 94th-minute winner at home to Portsmouth, having initially gone a goal down.
Callum Lang's first-half goal had Pompey ahead at half-time, but Jeremy Sarmiento equalised in the second period before Brownhill nicked a winner, leaving the Clarets third and Portsmouth second-bottom.
And Sheffield United are up to fourth after a 1-0 win over Derby County at Bramall Lane.
The Blades got the winner after 53 minutes through Gus Hamer, with Derby dropping to ninth on nine points from six matches.
Stoke entered this encounter at the bet365 Stadium just two points better off than their winless visitors and without reward for the bold decision to replace head coach Steven Schumacher with Pelach last month.
But an explosive display from on-loan Leicester City forward Cannon provided what could be a pivotal victory in the Potters' season.
Cannon scored only three times in all competitions for Leicester last term but bettered that tally inside the opening hour of his fourth start for Stoke.
Portsmouth were on level terms approaching half-time after Mark O'Mahony cancelled out Cannon's opener, but the Republic of Ireland international restored Stoke's lead before Sam Gallagher added a third in first-half stoppage time.
Cannon completed his hat-trick from the penalty spot three minutes after the restart and scored again another three minutes later, with Andrew Moran completing the rout shortly afterwards.
Portsmouth were promoted as League One champions last season but are the only team still without victory in the second tier and saw another struggling side move clear of them on Wednesday as Preston North End beat Watford 3-0.
Watford had been level on points with Sheffield United just outside the play-off places, but the Blades climbed to third with a 1-0 win over Swansea City, while rivals Sheffield Wednesday drew 0-0 with Bristol City.
