Nemanja Vidic played against his former club for Inter, but Manchester United prevailed on penalties to continue Louis van Gaal's impressive pre-season form.
Manchester United secured their third consecutive win under the Dutch tactician after victories against Los Angeles Galaxy and Roma.
Playing in their new blue third kit, United found a solid Inter solid who gave very few opportunities, but Inter 'keeper Samir Handanovic made an excellent diving save to keep out a Phil Jones header.
Van Gaal rotated his squad, beginning with Wayne Rooney and Danny Welbeck in attack but brought on Nani and Wilfried Zaha before replacing Nani with Javier Hernandez at the end.
Manchester United made eight changes at half time, but they dominated possession after the interval and looked the stronger side despite few clear-cut chances.
Zaha and Tom Cleverley both had possible penalty shouts but Inter could have stolen the win had David De Gea not made an excellent save from Fredy Guarin's 30-yard free-kick in the closing stages.
Ander Herrera looked sharp again and Zaha was full of life and gave the Inter defence some problems to deal with.
The game came down to penalties and Marco Andreolli made the fatal mistake for Inter while Ashley Young, Javier Hernandez, Tom Cleverley, Shinji Kagawa and Darren Fletcher converted for Manchester United.
Manchester United are top of Pool A in the Guinness International Champions Cup with five points, leading Roma and Inter who have three and are likely to reach the final which could be against Liverpool or Manchester City.
Manchester United: Lindegaard (De Gea 46), Smalling (Blackett 46), Jones (M Keane 46), Evans, Valencia (Shaw 46), Fletcher, Herrera (Cleverley 46), Young, Mata (Kagawa 46), Rooney (Nani 46, Hernandez 76), Welbeck (Zaha 46)
Inter: Handanovic (Carrizo 64), Ranocchia, Vidic (Andreolli 71), Juan Jesus, D'Ambrosio, Jonathan (Guarin 84), Kuzmanovic (Taider 64), Krhin (M'Villa 46), Dodo (Nagatomo 64), Botta (Laxalt 64), Icardi
Watch Manchester United beat Inter on penalties: