Goals in either half from David McGoldrick (45mins) and Daryl Murphy (63mins) condemned Millwall to a first away defeat of the season at Portman Road.
On an afternoon that had started with such promise for The Lions, McGoldrick opened the scoring deep in first-half injury-time with a deflected effort following a quick counter-attack from the home side.
Murphy doubled Town's advantage just past the hour mark, firing home from six yards after the visitors were caught out following a corner routine to secure only a second win of the season for Mick McCarthy's Tractor Boys..
Lions boss Ian Holloway made two changes that started against Blackpool two weeks previously, with Mathias Ranegie handed his full debut replacing Ricardo Fuller up front and Jermaine Easter filling the left flank in the absence of Lee Martin, sidelined with a knee ligament injury.
There was also a place on the bench for young goalkeeper Tom King in place of Denzel Gerrar who was also sidelined through injury.
Backed by a vociferous away crowd of around 1,300 fans and buoyed by a run of three wins in their opening five Championship, The Lions took to the field at Portman Road in confident mood.
With games coming up against Reading on Tuesday and the visit of Championship leaders Nottingham Forest to The Den next Saturday, manager Holloway was determined to see his side kick off a big week with a positive performance and result. Unfortunately it was not to be.
It was Ipswich who created the first chance of the game just before the two-minute mark when a long ball from Tyrone Mings picked out Murphy, who backed into Alan Dunne before lashing the ball yards wide of the target from just outside the penalty area.
Millwall were denied an opening goal on eight minutes. The two Scotts - McDonald and Malone - combined superbly down the left with the latter's over-lapping run into the heart of the penalty area catching the Ipswich back-line napping. Malone's low, square delivery picked out Martyn Woolford in a central position, but his goalbound shot was blocked by home keeper Dean Gerken, who eventually gathered the ball after Easter's follow-up smashed the bar and fell into his hands.
The Lions went close once more just before the quarter-hour mark when the rampaging Malone again slipped his marker and popped up in a dangerous position, this time laying the ball off for Easter who steadied himself before hitting a crisp shot straight into the arms of Gerken.
A delightful, patient move starting deep in the Millwall half and involving around 15 passes eventually came to an end with Ranegie steering his header from a Carlos Edwards' delivery wide of the target as the visitors continued to prose and probe looking for the opening goal.
Lions physio Bobby Bacic was called into action midway through the half to attend to Shaun Williams after the midfielder had been caught but a robust challenge from Mings that arguably warranted a yellow card from referee. When play resumed, and with Holloway's men temporarily down to 10 men, Ipswich created their best chance of the game when Paul Anderson's snap-shot from Jonathan Parr's cross was held by David Forde in the visiting goal.
Ipswich responded and Anderson again tried his luck, but what his effort packed in power, it lacked in precision and the ball sailed past Forde's post.
Woolford had a glorious opportunity to break the deadlock on 40 minutes but fired into the side netting after he was picked out by a neat threaded pass from Ranegie.
However moments later it took an outstanding save by Forde to thwart Ipswich at the other end, somehow getting his fingers to a texbook downward header from Murphy that was arrowing towards the top corner.
There was nothing Forde could do to prevent the home taking the lead deep in first-half injury-time though, as The Lions lost possession deep in the Ipswich half. Teddy Bishop drove forward and although he was fouled, play was waved on and McGoldrick picked up the ball on the right before hitting a shot that took a deflection on its way past Forde and into the back of the net.
Instead of using his half-time team talk based on a 0-0 opening first 45 minutes, Lions boss Holloway had to have a quick re-think as his side went in trailing 1-0, and at the start of the second period brought on Magaye Gueye for Jack Powell.
It took some great defending by Mark Beevers to just put McGoldrick off his stride as the Ipswich striker latched onto Murphy's inviting left-wing delivery, the striker firing wide from close range.
A move involving Gueye, Easter and McDonald looked promising, only for Malone's final cross from the left falling too close to Gerken in the home goal, and the keeper made a routine save at his near post.
The Lions found themselves 2-0 behind on 63 minutes when the team failed to deal with Jay Tabb's corner, Christophe Berra headed into the path of Murphy who lashed the ball into the roof of the net from close range.
McDonald was inches away from hauling Millwall right back into contention just 60 seconds with a sweet curling free-kick that Gerken tipped over for a corner.
Holloway made two changes soon after, bringing on Fuller and Ed Upson for Easter and Woolford in the 67th-minute minute, whilst former Lions boss McCarthy waited three minutes before making a double change with Tommy Smith and Luke Hyam replacing Mings and Bishop.
Millwall twice produced half-chances; captain Dunne's 25-yard piledriver was held by the keeper low to his left and then McDonald weaved his way into the danger zone before firing over.
Murphy directed a header from Luke Chambers' deep delivery wide of the target in reply and another strong block by Beevers again averted the danger as McGoldrick shaped to shoot.
Other than another McDonald effort that sailed harmlessly wide, Holloway's side were unable to reproduce the enterprising football that had served them so well in the first half, certainly until McGoldrick's opener, and Ipswich saw out the closing stages comfortably.
Ipswich Town: Gerken, Parr, Mings (Smith, 70mins), Chambers, Berra, Skuse, Murphy, McGoldrick, Anderson (Sammon, 81mins), Tabb, Bishop (Hyam, 71mins). Subs not used: Bialkowski, Bajner, Bru, Henshall.
Booking: Sammon (90+2mins)
Scorers: McGoldrick (45+2mins), Murphy (63mins)
Millwall: Forde; Edwards, Dunne, Beevers, Malone; Powell (Gueye, 46mins), Williams; Woolford (Upson, 67mins), McDonald, Easter (Fuller, 67mins); Ranegie. Subs not used: King, Briggs, Webster, Onyedinma.
Ref: C. Berry
Att: 16, 190 (away 1,329)