Fernando Santos' side, however, finished three points clear of Italy at the top of Group A3, after an unbeaten campaign despite the absence of star forward and captain Cristiano Ronaldo.
There was a lot of good interplay from the hosts with crisp, efficient passing in the best performance seen by an Italy side in a long time.
Belgium and Iceland were without several first-choice players on Thursday, but the home team showed it has a lot more strength in depth and dominated throughout the match.
Italy vs Portugal: Lorenzo Insigne in spotlight as Azzurri look to bury World Cup demons in San Siro
A year on and the versatile 27-year-old has become an integral part of the new Italy side being built by coach Roberto Mancini, which is fighting for a place in the Nation's League semi-finals.
Tin Jedvaj scored his second goal three minutes into stoppage time to earn Croatia a 3-2 victory and a first win in a competitive match since beating England in the World Cup semifinals.
Luka Modric's squad will include three young players: forwards Josip Brekalo and Nikola Vlasic as well as defender Duje Caleta-Car.
But La Roja were dealt a reality check, losing 3-2, as England ran riot during a whirlwind first half in Seville.
Recent defeat to the Dutch left Germany bottom of their Nations League group, fuelling questions about whether he should have retained his job after the humiliating early exit from the World Cup.
Luis Enrique Spain's can secure top spot in Group 4 with a win, having already beaten England 2-1 at Wembley last month
The 29-year-old had hoped to recover for his country's trip to Dublin on Tuesday, but Wales manager Ryan Giggs had already admitted he didn't expect the forward to be back in time.
This is the first time the Dutch have beaten Germany for 16 years and the comprehensive defeat leaves Loew under increasing pressure to resign after 12 years in charge.
Belgium's second win of the fledgling tournament keeps them flying high in League A Group 2 following an opening 3-0 win in Iceland.
His former captain Michael Ballack turned on him this week, claiming he was "surprised" Loew kept his job in the wake of Germany's World Cup debacle when they crashed out after the group stage.
Fernando Santos's Portugal team now have two wins in two in the Nations League after also beating Italy 1-0 in September.