Although it is unclear how long the film takes place after Despicable Me 2, it can be reasoned that very little time has passed between the two movies. There are several pieces of evidence that support this claim such as the fact that the girls surprised Gru and Lucy with a Hawaiian luau style party for their "honeymoon". Additionally, Lucy's personal conflict within the film was discovering herself as a new mother to the girls, suggesting that a very small amount of time passed between the end of the second film and the beginning of the third film.
This film marks Trey Parker's first role in a children's film.
The film is notably different from how the movies usually go:
It doesn't start at a random country whereas something important happens that might later occur.
Gru appears at the beginning of the film rather than later.
The title appears after appearance of several scenes.
The font used in the credits is different. On a related note, the animated credits sequence is also different as well.
Marlena Gru plays a larger role than she had in the first film.