The Tractors Boys came into this midweek clash possessing an 11-game unbeaten streak across all competitions, however defeat for the hosts looked a distinct possibility from very early on when Harry Wilson put the Cottagers ahead inside 10 minutes.
Rodrigo Muniz doubled the Premier League side's advantage in the opening stages of the second period and Tom Cairney bagged a third to secure the win, however Ipswich did manage to net a consolation in the final moments of the match courtesy of substitute Elkan Baggott.
With the visit of Manchester United at Saturday lunchtime in the forefront of Marco Silva's mind, Fulham made eight changes to the side who drew at Brighton & Hove Albion on Sunday, with only Bobby Reid, Calvin Bassey and Timothy Castagne maintaining their starting berths for this fourth-round clash.
Ipswich named a completely-different XI to the one which dramatically beat Plymouth Argyle in the Championship on Saturday, with goalkeeper Christian Walton earning his first start of the campaign, whilst centre-back Axel Tuanzebe appeared in a competitive fixture for the first time since March when he was on loan at Stoke City.
Having won 11 of their 13 matches during their sensational return to the second tier so far, the Tractor Boys were looking to bring the game to their Premier League opposition in the opening stages, but Kieran McKenna's side were caught desperately on the break, allowing Fulham to take control of the contest.
After some brilliant hold-up play from Muniz, the Brazilian found Reid in the middle of the park, and the former Bristol City man looked up quickly to see Wilson in acres of space on the right flank at Portman Road, having escaped the attention of left-back Harry Clarke for the hosts.
The Welshman was sent through on goal by his teammate and skipped past the onrushing Walton - who in truth would have been better staying closer to his goal - and the 26-year-old finished calmly into an empty net from just outside the box, bagging his first goal of the 2023-24 campaign.
Despite going behind early on, Ipswich did not let the setback impact their efforts to bring the game to the Cottagers, and right-back Janoi Donacien - starting only his fourth game of the season - had a shot which failed to worry Marek Rodak in the visitors' goal, yet proved the Championship side could venture into dangerous areas.
After taking a one-goal lead into the changing rooms at Portman Road, Fulham were quick out of the traps in the second period, and a delicious cross from Andreas Pereira allowed Muniz to get onto the scoresheet during only his third start of the term, with Mexican striker Raul Jimenez being Silva's preferred option in the Premier League.
Former Man United man Pereira picked up the ball on the right flank and swung a low cross into a dangerous area between the Tractor Boys' backline and keeper Walton, and 22-year-old Muniz managed to ghost into the corridor of uncertainty to tap home his team's second of the evening.
Now having 40 minutes to score at least twice against first-tier opposition, Ipswich strangely opted to shuffle their defence, with centre-back Cameron Burgess being replaced by Baggott, suggesting that head coach McKenna had Saturday's trip to Birmingham City in the Championship in mind.
Attacking substitutions did arrive for the hosts in the form of striker George Hirst and Chelsea loanee Omari Hutchinson, however the Tractor Boys' exit from the competition was essentially confirmed after a long-serving Fulham star put the Cottagers three goals ahead in the 77th minute.
Following a clearance from right-back Castagne, Jimenez sent attacker Reid racing down the right, and the 30-year-old bagged his second assist of the game when his pass found Cairney, who punched a shot towards Walton's net, with the returning keeper unable to keep the ball from sliding under his body and into the goal.
The hosts grabbed a consolation just two minutes later through substitute Baggott, who found himself completely unmarked from a corner-kick and headed in Jack Taylor's inswinging delivery, although the result of the contest was already settled at this point.
Ipswich's loss in this EFL Cup fixture represents only their second defeat in all competitions so far in 2023-24, with McKenna's boys last tasting defeat after a dramatic seven-goal thriller with recently-relegated Leeds United in the Championship on August 26.
The Tractor Boys' supporters will not be too concerned about their performance this evening considering that they made 11 alterations to their starting XI, and fans should fully expect the raft of fringe players to return to the bench when the East Anglian club travel to face Birmingham City in the second tier on Saturday.
After winning a fixture away from Craven Cottage for the first time since the opening-day success at Goodison Park against Everton, Fulham will be looking to record back-to-back wins when they welcome Erik ten Hag's Red Devils to West London on the weekend, with the Cottagers having the chance to leapfrog their visitors.