First-half goals from Goran Pandev and Samuel Eto'o and a late strike by substitute Jonathan Biabiany gave the Italian team their third world title after they won the former Intercontinental Cup in 1964 and 1965.
It was the fourth time in a row a European team has won the tournament - although UEFA's representatives had eight South Americans and one African in their starting line-up.
Mazembe, from Democratic Republic of Congo, were the first team from outside Europe or South America to reach the final since the tournament was started in its current format in 2005.
The win was a welcome break for Benitez whose side are a modest seventh in Serie A, 13 points behind leaders and arch-rivals AC Milan, and only just squeezed into the knockout stages of the Champions League.
Pandev sent Inter on their way when he ran onto a fine pass by Eto'o to slip the ball past goalkeeper Muteba Kidiaba and open the scoring in the 13th minute.
Four minutes later, Cameroon striker Eto'o broke through on his own to steer the second past Kidiaba, who had kept clean sheets for the African champions in their previous two matches.
Biabiany beat the offside trap to reach a long pass out of defence and round Kidiaba for the third in the 85th minute.
"We are a true team," Pandev told reporters. "When it counts we don't make a mistake.
"Eto'o gave me a great pass for my opener. Today we've played a great game. Since I arrived (in January) we've won five trophies. That ain't bad!"
Inter striker Diego Milito, whose goals helped secure last season's treble of Serie A, Italian Cup and Champions League, twice had chances to score when he found himself alone with only Kidiaba to beat but both times he was foiled.
Mazembe, who impressed with wins over Pachuca on Mexico and Brazil's Internacional on their way to the final, had their chances, not least when Ivan Cordoba dived to block a Dioko Kaluyituka effort.
Kaluyituka, who brought a late point-blank save from Julio Cesar, and strike partner Mulota Kabangu caused the Inter defence a few scares with their speed on the flanks.
Eto'o, who had a brilliant game against his fellow Africans, might have scored again but for a good save by Kidiaba.
