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Harewood's brace and goals from midfielder Gary Taylor-Fletcher and defender Alex Baptiste gave the visitors their first away win among the elite since the last time they graced the top flight with a win over Newcastle on August 29 1970.
The defeat suggests that last year's worst Premier League defence - they let in 79 goals - is going to be equally generous this time round.
Blackpool got a dream start after a close season which saw manager Ian Holloway struggling to get a full 25-man squad together and building work at their stadium meaning they had to ask Wigan if they could switch the match to their ground.
Taylor-Fletcher, who began his career playing non-league football with Northwich Victoria, was found by Harewood, one of Holloway's six signings this week, and the 29-year-old midfielder stroked the ball home.
Harewood, who was released by Aston Villa at the end of last season, was in good form and forced Wigan 'keeper Chris Kirkland into a smart save in the 26th minute.
However, the former Nottingham Forest and West Ham marksman was not to be denied 12 minutes later as he put the newboys 2-0 up.
Five minutes later the 30-year-old doubled his tally by tapping into an empty net after Kirkland has beaten away Frenchman Elliott Grandin's shot.
The tempo dipped after the break and Harewood went off on the hour mark as Holloway sought to solidify the midfield bringing on another of the new intake, former Bolton Wanderers midfielder Chris Basham.
Wigan did at least start to trouble Blackpool 'keeper Matthew Gilks as summer signing Mauro Boselli had a header saved and put another one wide within two minutes shortly after Hugo Rodallega had a shot brilliantly saved.
However, there was no stopping Blackpool and Baptiste - formerly of Mansfield Town and who had a loan spell with non league side Tamworth -put them 4-0 up in the 75th minute with a stunning long range effort from 30 yards out.
It should have been 5-0 by the end as veteran striker Jason Euell was cursing himself after seeing his header repelled by Kirkland but straight back to him, however, the 33-year-old former Wimbledon marksman could only shoot wide.
