Danielle Wyatt scored 41 and Sarah Taylor hit six boundaries in her 35 as the home side scored 162-7 in their 20 overs.
Laura Marsh then claimed two for 15 as Pakistan were restricted to 81 for five, with Wyatt, Katherine Brunt and Jenny Gunn taking a wicket apiece.
“It was another good team performance today, we got the runs on the board and put them under pressure with the ball," said Danielle Wyatt, who won the player of the match award.
"I was pleased to contribute and it was very satisfying to set a new highest score. We’ll take momentum from these matches into the series against the West Indies."
England won the first match, also at Loughborough, by seven wickets on Wednesday.
England knocked off the target of 88 with 25 balls to spare, with Taylor and Arran Brindle (not out) topscoring with 31 apiece.
England will play the West Indies over five T20 matches, beginning in Durham on Saturday September 8.