The South American section of the 2022 FIFA World Cup qualification acted as qualifiers for the 2022 FIFA World Cup, to be held in Qatar, for national teams which are members of the South American Football Confederation (CONMEBOL). A total of 4.5 slots (4 direct slots and 1 inter-confederation play-off slot) in the final tournament were available for CONMEBOL teams.

The qualification process began on 8 October 2020 and ended on 29 March 2022. Uruguay's Luis Suárez scored the first goal of the round-robin. This was the third time Suárez had opened scoring in the group (after 2010 and 2014), as well as the fourth consecutive time a Uruguayan player had done so (Martín Cáceres scored the first goal of the 2018 process).

On 24 January 2019, the CONMEBOL Council decided to maintain the same qualification structure used for the previous six tournaments. The ten teams play in a league of home-and-away round-robin matches.

The fixtures were determined by a draw which was held on 17 December 2019, 10:00 PYST (UTC−3), at the Bourbon Asunción Convention Hotel in Luque, Paraguay.

Originally, Brazil and Argentina were both to be drawn into either position 4 or 5 in the draw, thus ensuring that no team has to play both of them on any double matchday. However, the decision was later reversed on 16 November 2019 by the CONMEBOL Council, making the draw completely open.

The CONMEBOL Council approved the use of the video assistant referee system for the qualifiers.

All 10 national teams from CONMEBOL entered qualification.

Note: Bolded teams qualified for the World Cup. Peru advanced to the inter-confederation play-offs.