The plans will add around 7,000 new seats to the stadium as well as a new covered fan zone, club shop, museum and 400-bed hotel.
Last week, the Etihad was included on the list of 10 stadia which would host matches if the UK and Ireland's joint bid for organising Euro 2028 is successful, with the bid quoting a planned new capacity of 61,000.
"Over several months we have been developing concepts and designs for a best-in-class fan experience and year-round entertainment and leisure destination at the Etihad Stadium and are delighted to have now submitted a planning application to Manchester City Council," said City's managing director of operations Danny Wilson
"As with all club developments, ensuring our local community benefit is a key priority and we believe these proposals will deliver long-term economic and social opportunities, building on the regeneration work delivered in East Manchester by City Football Group since 2008."
Since an Abu-Dhabi backed takeover 15 years ago, the area around the Etihad has been transformed.
The Etihad Campus, which comprises the club's training ground and office headquarters, opened in 2012 and a previous expansion of the Etihad's south stand was completed in 2015.