Five-time champion Brazil had been left waiting in suspense after goals from Neymar, Philippe Coutinho and Marcelo handed them a 3-0 win over the Paraguayans at Sao Paulo's Arena Corinthians.
But Uruguay's upset 2-1 defeat to Peru in the day's final South American qualifier combined with other results meant Brazil are mathematically guaranteed a place at next year's finals in Russia.
The qualification completes an astonishing turnaround for Brazil, who less than a year ago were in crisis after taking only nine points from six games.
That run of results had left the Brazilians outside the qualifying places in sixth place.
The further embarrassment of a first round exit at last year's Copa America Centenario only deepened the sense of despondency.
However the sacking of former coach Dunga and the appointment of former Corinthians coach Tite was the catalyst for a Brazilian resurgence.
That revival saw Brazil take maximum points from their next eight qualifying games, leaving them nine points clear on Tuesday with four games left.
Against Paraguay, Brazil were already in party mode, with Coutinho opening the scoring on 34 minutes following a deft one-two with China-based midfielder Paulinho.
Neymar had a chance to make it 2-0 in the 53rd minute from the penalty spot only to see his kick saved by Anthony Silva.
On 64 minutes Neymar doubled Brazil's tally, collecting the ball deep inside his own half and setting off on a surging run down the left flank.
Neymar's dribble ended with him curling in a shot which took a slight deflection on its way into the Paraguayan goal. Real Madrid defender Marcelo added a late third to seal Brazil's win.
[caption id="attachment_55241" align="aligncenter" width="640"]
Brazil's Marcelo about to score his side's third goal against Paraguay in Sao Paulo REUTERS
While Brazil celebrated, Argentina and Messi were left digesting another stumble in their progress towards Russia as they slumped to a 2-0 defeat in La Paz.
Argentina had been rocked just hours before kick-off after confirmation Messi had been hit with a four-match ban following a ruling from disciplinary chiefs at world governing body Fifa in Zurich.
The Barcelona superstar was stunned after being suspended for four of Argentina's five remaining World Cup qualification matches for swearing at an official in a game against Chile last week.
Messi's suspension left Argentina coach Edgardo Bauza forced to make a hasty reshuffle to his starting line-up, bringing in Atletico Madrid's Angel Correa in attack while leaving Manchester City's Sergio Aguero on the bench.
But Argentina, clearly struggling in the thin air of La Paz, which is 3,600 metres (11,800 feet) above sea level, were well beaten at the Estadio Hernando Siles.
Bolivia, desperate for three points, tore into Argentina from the opening whistle, spending long periods camped around their opponent's area.
Juan Carlos Arce opened the scoring for Bolivia on 31 minutes, heading in Pablo Escobar's inviting cross before Marcelo Martins doubled the home side's lead early in the second half.
The defeat leaves Argentina languishing just outside the automatic qualifying places following results elsewhere Tuesday.
Chile moved up to fourth place with a 3-1 win over Venezuela in Santiago, Arsenal star Alexis Sanchez opening the scoring with a stunning early free-kick. Esteban Paredes scored twice for Chile to give the host a 3-0 lead before Salomon Rondon pulled a goal back for Venezuela.
In Quito, Real Madrid star James Rodriguez scored one goal and set up another for Juan Cuadrado as Colombia beat Ecuador 2-0.
(Coutinho 34, Neymar 64, Marcelo 85) Paraguay 0
(Arce 31, Martins 53) Argentina 0
Ecuador 0 Colombia 2
(Rodriguez 20, Cuadrado 34)
(Sanchez 4, Paredes 7, 22) Venezuela 1
(Guerrero 35, Flores 62) Uruguay 1