The 36-year-old Inter Miami forward scored a brace in Argentina's 2-0 win over Peru last month, increasing his international goal tally to 106, and he is expected to walk out for the 179th time in front of the La Bombonera crowd in Buenos Aires.
Julian Alvarez and Nicolas Gonzalez both started in attack alongside Messi against Peru and they could keep their places in the front three, although Lautaro Martinez, Paulo Dybala and Angel di Maria will all be hoping to force their way into the first XI.
Messi was not the only award winner at the Ballon d'Or ceremony last month, as Aston Villa goalkeeper Emiliano Martinez became the 15th winner of the Yashin Trophy, and he is set to continue between the sticks on Thursday.
Nicolas Otamendi, one of three players in Lionel Scaloni's 27-man squad to have earned over 100 international caps, could link arms with Cristian Romero at centre-back, while Mallorca's Spanish-born defender Pablo Maffeo has received his maiden international call-up to the Argentina squad, and the 26-year-old will battle with Nahuel Molina and Gonzalo Montiel for a start at right-back.
Olympiakos left-back Francisco Ortega is another newcomer to the Argentina squad and he will compete with Nicolas Tagliafico and Marcos Acuna for a place in Thursday's first XI.
Alexis Mac Allister, Enzo Fernandez and Rodrigo De Paul appear to be the first-choice midfield triumvirate for Scaloni, but Leandro Paredes, Guido Rodriguez, Exequiel Palacios and Giovani Lo Celso are all in contention to feature against Uruguay.
Argentina possible starting lineup: E. Martinez; Molina, Romero, Otamendi, Tagliafico; Mac Allister, Fernandez, De Paul; Messi, Alvarez, Gonzalez