The Azzurri have now won 15 of their 20 matches since a 1-0 Nations League loss to Portugal in September 2018 and they never looked in danger of tasting defeat against a side 97 places beneath them in the world rankings.
Led by Alberico Evani with Roberto Mancini self-isolating after testing positive for COVID-19, the hosts went ahead after 14 minutes courtesy of Grifo's maiden Italy goal and Federico Bernardeschi doubled their advantage.
Grifo then added a second from the penalty spot in the 75th minute before substitute Riccardo Orsolini added another from 12 yards to help Italy wrap up the most routine of wins.
Freiburg forward Grifo marked his fourth appearance for Italy with a sumptuous opener, whipping a half-volley in off Marko Meerits' left-hand post from 25 yards after a lay-off by Kevin Lasagna.
An unmarked Lasagna missed a glorious chance soon after, the Udinese forward failing to make a clean connection with Bernardeschi's teasing cross from close range.
Italy's dominance was rewarded shortly before the half-hour mark, though, when Bernardeschi cut in from the right to bend a left-footed strike into the bottom corner from just outside the penalty area – his first international goal since October 2019.
Emerson Palmieri lashed wide following an incisive move on the edge of the penalty area after the interval, while Grifo saw an effort deflected narrowly wide.
Grifo got his second when he thumped home from 12 yards after Roberto Gagliardini was tripped inside the penalty area by substitute Georgi Tunjov.
Orsolini then wrapped up the scoring in the 86th minute, sweeping home his second international goal from the spot after forcing Henri Jarvelaid into a rash challenge in the area.