Manchester United's bid to win the Europa League begins in the Netherlands on Thursday when they travel to Ajax Amsterdam.
Alan Kardec opened the scoring for hosts Santos within 60 seconds of the kick-off at Estadio Urbano Caldeira.
Vinicius doubled the lead on 58 minutes, before Marcelo pulled one back for Linense with 20 minutes remaining.
But if the visitors had any brief hopes of mounting a comeback, they were swiftly crushed.
Within minutes of Marcelo's goal, first Anderson Carvalho and then Felipe Anderson scored to make it 4-1 to the home side.
The win, Santos' third from seven matches played this season, lifts them up the sixth place on the table, five points back from leaders Palmeiras.
Elsewhere, a 21st-minute strike from Danilo was enough for Corinthians to see off Sao Paulo 1-0 at home.
The visitors missed a chance to equalise when striker Jadson failed to convert his penalty a minute before the break, and they finished a man down after Joao Felipe was shown a red card just before the hour mark.
In other matches, Jose Fernando Fumagalli's 75th-minute spot kick helped Guarani beat Paulista 2-1 at home.
Tadeu was on target for Oeste with 10 minutes remaining as they defeated Guaratingueta by the same scoreline.
Goals from Luis Ricardo and Renato, together with Da Silva Leonardo Moura's penalty, saw Portuguesa de Desportos ease to a 3-0 win at home to Botafogo.
Sao Caetano had Marcelo's brace to thank for their 2-0 victory over visiting Comercial.
Finally, Diniz and Dairo both scored as Catanduvense ran out 2-0 winners in their match away to XV de Novembro.
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