The Giants (5-2) trailed the entire game until Manning engineered a six-play, 53-yard drive in the final quarter, capped by his go-ahead scoring pass over the middle to Cruz.
Manning completed 31-of-45 pass attempts for 349 yards and a pair of scoring strikes with no interceptions for the Giants, who were coming off a bye week.
Cruz ended with seven caches for 99 yards and Lawrence Tynes went 2-for-2 on field goal tries in the victory.
Matt Moore managed just 138 aerial yards on 13-of-22 passing efficiency and ran in a touchdown for the Dolphins (0-7), who dropped their 10th straight game dating back to last season.
2014: The Year in Fashion [PHOTOS]
UPI Sports Results for September 19, 2014