Grimsby Town suffered a third defeat in a row as Leyton Orient won comfortably at Blundell Park.
The Mariners fell behind on 11 minutes when Daniel Happe opened the scoring and the visitors doubled their lead 10 minutes later through Josh Coulson as both centre-backs got on the scoresheet.
After a double-substitution at half-time, Town started to create more chances, with James Hanson and Elliott Whitehouse both going close to halving the deficit.
But they were punished for not converting those opportunities, as substitute James Alabi made it 3-0 to the away side before Josh Wright added a fourth from the penalty spot.
Manager Michael Jolley made five changes to his Town starting line-up after last week's defeat at Stevenage, with Ludvig Ohman, Liam Gibson, Harry Clifton, Charles Vernam and Ahkeem Rose all coming into the XI.
James McKeown started in goal, with Luke Hendrie, Ohman, Luke Waterfall and Gibson forming the defence.
Clifton, Jake Hessenthaler and Elliott Hewitt were the midfielders, with Vernam and Rose lining up either side of Hanson in attack.
Harry Davis, Whitehouse, Matt Green and Jordan Cook were all named on the bench having started the game last week and they were joined as substitutes by Moses Ogbu, Sam Russell and Mattie Pollock.
The visitors included four players who had previously featured for the Mariners, with Joe Widdowson, Craig Clay and Matt Harrold starting the game and Alabi among the subs.
They began the day 17th in League Two but knew a win would take them above Town, who sat in 10th place at kick-off.
The hosts won an early corner when a cross from Rose on the left was ruled to have taken a deflection but the referee's whistle blew for an Orient free kick as Gibson's delivery came across.
A foul by Hendrie gave the away side a free kick on the left after a good spell of possession but Wright's ball into the penalty area was headed away by Gibson.
Town's respite proved only brief though as the ball was worked back into the box and after McKeown made a save from his first effort, HAPPE sent the rebound into the net to put Orient ahead.
Harrold won a corner on the right as the visitors continued to look the better of the two sides at the quarter-hour mark but this time, the ball was fully cleared.
A good challenge by Waterfall inside his own penalty area stopped a run by James Brophy on 19 minutes.
But the next time they went forward, Orient doubled their advantage. James Dayton was bundled over midway inside the Town half and after the Mariners failed to deal with Wright's delivery from the free kick, COULSON hooked a volley past McKeown and into the net.
Grimsby had an opportunity to pull a goal back when Rose and Hessenthaler linked up well but the midfielder's shot was saved by keeper Dean Brill and Ohman was penalised for a foul as the resulting corner came over.
Hendrie was shown the first yellow card of the game after bringing Brophy down near the halfway line but the Mariners broke after the free-kick and Hanson won a corner at the other end, which was cleared.
Harrold was booked for a foul on Clifton, before a foul on Hanson gave Town a free kick on he left but Gibson's ball was cleared.
The Mariners were struggling to seriously threaten Brill's goal as the half-hour passed, with the visitors looking comfortable.
Dayton and defender Marvin Ekpiteta were both booked for time-wasting over a throw-in on 37 minutes, then Town won a corner four minutes later but were unable to turn it into a goalscoring opportunity.
Three added minutes were played at the end of the half but Town were not able to threaten further and the visitors held their two-goal lead at the interval.
Ogbu and Green replaced Clifton and Vernam before the restart and the substitutes combined five minutes in when Ogbu's cross from the right found Green at the near post but his volley was well-saved by Brill and the ball was put out for a corner.
Hewitt became the latest to see the referee's yellow card after a trip on Brophy, before Louis Dennis replaced Dayton as the away side made their first change.
Ogbu was fouled on 58 minutes and the referee initially let him continue before bringing play back for a free kick, which eventually led to a corrner on the left. Whitehouse came on for Hewitt before the flag-kick was taken and cleared.
The away side should have put the result beyond doubt on the hour when Brophy got to the by-line on the left and pulled the ball back for Dennis but he failed to find the net when unmarked, eight yards out.
Another opportunity for Orient came soon afterwards but Clay's curling, 20-yard effort was pushed away for a corner by McKeown at full-stretch.
Hanson was unable to connect with a Hendrie cross after good play by Green on the right as the home side looked for a way back into the contest.
They almost had it on 67 minutes when Hendrie sent a great low ball across the six-yard line from the right but Hanson could only send it over the bar.
And another great chance came and went unconverted when the ball was chipped into the box from the right but Whitehouse planted his header wide from close range.
Alabi was sent on in place of Harrold in the Orient attack and the final substitution of the game saw George Marsh replace Dale Gorman.
A corner for the visitors almost produced a third goal as the ball broke for Coulson but Rose got back to block his shot on the line.
Clay and Brophy linked up well as Orient attacked again but the ball was cleared for a corrner.
A free-kick from Gibson at the other end was headed away at the far post and soon afterwards, the game was over as a contest as the visitors grabbed a third goal. Town lost possession in midfield and ALABI ran through from halfway before keeping his composure to slot past McKeown.
And it was to get worse for Town when Waterfall tripped Alabi inside the box on 84 minutes and the referee pointed to the penalty spot. WRIGHT stepped up and calmly slotted into the net as McKeown went the wrong way.
Three added minutes were played before the referee's final whistle brought an end to the game, with the Town fans going home disappointed after a heavy loss.
The Mariners are next in action on Tuesday, when they travel to Cambridge United.
Town: McKeown: (C), Hendrie, Gibson, Waterfall, Öhman, Hessenthaler, Hewitt, Clifton, Hanson, Vernam, Rose.
Subs: Russell, Davis, Pollock, Cook, Whitehouse, Green, Ogbu.
Leyton Orient: Brill, Ekpiteta, Widdowson, Coulson, Happe, Wright, Dayton, Clay, Brophy, Harrold, Gorman.
Sargeant, Judd, Ogie, Maguire-Drew, Marsh, Alabi, Dennis.
Referee: Nicholas Kinseley
Attendance: 4132 (383)
Possession: Town 56% - 44% Leyton Orient
Corners: Town 6-4 Leyton Orient
Next Up: Cambridge Utd (A)