The No 10-ranked Gastelum (16-8, 1 NC) has lost five out of his last six, most recently suffering a decision defeat to top contender Jared Cannonier.
His only win since 2019 is a decision over Ian Heinisch.
Du Plessis (16-2) joined the UFC over a year ago following stints under KSW and EFC banners.
The 28-year-old has earned finishes in both Octagon appearances, knocking out Markus Perez and Trevin Giles at UFC Fight Island 5 and UFC 264, respectively.
All of Du Plessis’ 16 wins have come via stoppage, and he’ll be going up against a foe in Gastelum who’s never been knocked out and only submitted by Jack Hermansson and Chris Weidman.
Leading South African bookmakers Hollywoodbets have installed Gastelum as a 61/100 favourite, with Du Plessis on offer at 23/20.
UFC 273 will take place in Jacksonville, Florida on Saturday, 9 April with a main event between featherweight champion Alexander Volkanovski and Chan Sung Jung aka ‘The Korean Zombie’.
Men’s bantamweight champion Aljamain Sterling will face former champion Petr Yan in a co-main event rematch.
Updated UFC 273 line-up:
Alexander Volkanovski v Chan Sung Jung – for featherweight title
Aljamain Sterling v Petr Yan – for bantamweight title
Gilbert Burns v Khamzat Chimaev
Mackenzie Dern v Tecia Torres
Irene Aldana v Aspen Ladd
Ian Garry vs. Darian Weeks
Dricus du Plessis v Kelvin Gastelum
Jairzinho Rozenstruik v Marcin Tybura
Ilir Latifi v Aleksei Oleinik
Mickey Gall v Mike Malott
Pat Sabatini v Gavin Tucker
Julio Arce v Daniel Santos
Mark Madsen v Vinc Pichel
Kay Hansen v Piera Rodriguez
Josh Fremd v Anthony Hernandez
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