The title also means that Napoli head coach Antonio Conte becomes the first coach to win Serie A with three different clubs after previous Italian league trophies with Inter Milan and Juventus.
Napoli led defending champions Inter by one point entering the final round of fixtures that was played simultaneously and it briefly looked like the title might be staying in Milan in the first half.
Inter took the lead over Como in the 20th minute but Napoli made sure they were not going to be denied after goals by Scott McTominay and Romelu Lukaku.
Former Manchester United player McTominay gave the hosts the lead in the 42nd minute when he struck a superb volley from a Matteo Politano cross, his 12 goal of the season.
Napoli doubled their advantage early in the second half after Lukaku finished off a brilliant solo effort that saw the forward beat two defenders.
It is Napoli's second league success in three seasons after they ended a 23-year wait for the title in 2023 and sparked wild celebrations at the Stadio Diego Armando Maradona, the stadium named after the Argentina great who led the club to their first two league titles in 1987 and 1990.
Inter also won 2-0 against 10-man Como thanks to goals by Stefan de Vrij and Joaquin Correa but will have to settle for second place in Serie A.
The Milan club could still finish their campaign in glory as they have the UEFA Champions League final to look forward to where they play Pars St-Germain on 31 May in Munich.