Grimsby Town stunned Championship top-flight Luton to reach the fifth round of the FA Cup for the first time since 1996.
Harry Clifton, whose equalizer at Kenilworth Road earned the replay, gave the League Two side an early lead with a powerful strike.
Danilo Orsi’s half-volley doubled the lead before a Danny Amos free-kick gave the Mariners a 3-0 lead at half-time.
Goalkeeper Max Crocombe then made a series of saves to secure a trip to Southampton on Wednesday March 1.
Despite 60 places separating the sides, the Mariners had already knocked out League One sides in this season’s cup, including a 5-1 demolition of promotion-seeking Plymouth Argyle.
Grimsby are currently 16th in League Two, nine points from the drop zone and play-offs, but will line up in the last 16 against Premier League opposition as the lowest-seeded side.
Luton boss Rob Edwards made six changes from the starting XI which beat Stoke to finish fourth in the Championship on Saturday, but five from that side have been named on the bench.
They looked like they needed a lifesaving act after just nine minutes, however, when Orsi burst into the box and tackled Clifton whose left-footed strike beat Hatters keeper Ethan Horvath.
Clifton then turned provider, sending a throw-in to Orsi whose half-volley found the bottom corner, and an upset looked unlikely when Amos whipped a left-footed free-kick onto the post.
It capped a nightmarish first half for the visitors who were firmly second and only created one decent chance, at 2-0, when Elijah Adebayo’s header, after Gabriel Osho’s run, was prevented by the beautiful stop of Crocombe.
After a double substitution from Luton at half-time, Crocombe somehow prevented Cauley Woodrow’s close-range header early in the second half, and Edwards made two more attacking substitutions before the hour mark in an attempt to trigger a return.
Crocombe went down well to his left to stop Luke Berry’s drilled shot, then denied Carlton Morris as substitute Alfie Doughty and Woodrow caused problems.
But the resilient Mariners handled the game well, and as the threat from the visitors began to fade, Bryn Morris nearly made it 4-0, putting his full-back effort inches wide.