Icardi had been without a league goal since January 5, but at his old stomping ground he exploded back into life, becoming the sixth-youngest player to reach 100 goals in Serie A and blowing Sampdoria away in an extraordinary performance.
It took Inter a little while to find their stride, but once they went ahead through Ivan Perisic – scoring for the first time since December 3 – there was no looking back, as they blitzed Sampdoria before the break.
Icardi was central to a stunning first-half showing, netting his milestone goal from the penalty spot before completing a 14-minute hat-trick with a pair of close-range finishes including an impudent backheeled effort.
The Inter captain was not finished there, though, scoring his fourth of the day just after the break thanks to a stroke of good fortune.
Antonio Candreva should have added a sixth late on, but that mattered little in the grand scheme of the game, as Inter cruised to a fantastic win and moved back up to fourth ahead of Lazio for at least a few hours.
Proceedings were cagey and pedestrian at first, but things soon livened up in the 21st minute when Inter's onslaught began.
Samp goalkeeper Emiliano Viviano suddenly became very busy, producing smart saves to deny Perisic and Milan Skriniar, before a Joao Cancelo corner struck the post.
Viviano was helpless soon after, however, as Perisic met Cancelo's cross with a looping header from the edge of the box and found the right side of the net.
Rafinha was then hauled down by a clumsy Edgar Barreto challenge in the 30th minute, with Icardi coolly dispatching the resulting penalty to reach his landmark.
The striker will have perhaps wished his second of the day was the milestone goal, as he beat Viviano with an audacious backheel.
And he rounded off his stunning first half on the stroke of half-time, blasting into the roof of the net from five yards after Viviano had denied Rafinha.
Fortune smiled on Icardi five minutes after the break, as he produced a volley from a tight angle that was drilled into the ground and bounced over the helpless Viviano for his 100th goal in an Inter jersey.
Sampdoria sat back even further as a result in an attempt to limit the damage, and their hopes of not conceding further goals were improved when Icardi went off for Eder – also facing his former side – in the 66th minute.
Candreva should have rounded things off 13 minutes from the end by ending his 11-month goal drought, but Gianmarco Ferrari raced back to block his 12-yard effort following a precise Perisic cutback, though the scoreline had long since lost any degree of respectability by that point.
