Carlo Ancelotti's side held a two-goal lead at halftime thanks to strikes from Dries Mertens and Kostas Manolas, but Balotelli pulled one back as Brescia rallied after the break.
Juventus slumped to another surprise defeat on Wednesday when the champions lost 1-0 at Sassuolo while AS Roma reclaimed top spot in Serie A with a 3-1 home victory over Udinese.
Barcelona coach Ernesto Valverde's conservatism was cited by the Spanish media as the main reason for their 3-0 defeat at AS Roma on Tuesday that led to a shock Champions League quarter-final elimination being regarded as 'a historic debacle'.
AS Roma needed a penalty from 40-year-old forward Francesco Totti in the seventh minute of stoppage time to scrape past second-tier Cesena 2-1 in their Coppa Italia quarter-final on Wednesday.
Manchester City qualified for the knockout stages of the UEFA Champions League with goals from Samir Nasri and Pablo Zabaleta sinking Roma 2-0 to eliminate the Italians.
Barcelona capitalised on two disastrous own goals by A S Roma to thrash the Italian side 4-1 at the Nou Camp on Wednesday and take a huge step towards reaching the Champions League semi-finals for the first time in three years.
AS Roma pulled off one of the great Champions League comebacks by knocking Barcelona out with a remarkable 3-0 win in their quarter-final second leg on Tuesday, overcoming a 4-1 deficit from the first game to reach the last four on away goals.
Later on Monday, Lukaku's brace helped Inter to a win over Napoli, taking them atop the standings on goal difference from Juventus.
Croatia edged closer to next year's World Cup with an emphatic 4-1 home win over Greece on Thursday in the first leg of their two-legged playoff.
A round-up of Saturday's action in Serie A, La Liga and Bundesliga.
Manchester United goalkeeper David de Gea added another heart-stopping save to his collection as his team held a highly-impressive Sevilla side to a 0-0 draw away from home in the first leg of their Champions League last-16 tie on Wednesday.
Real Madrid's Cristiano Ronaldo was the scourge of AS Roma again as he inspired the hosts to a 2-0 win and a place in the Champions League quarter-finals on Tuesday, scoring and setting up a goal Rodriguez to seal a 4-0 aggregate victory.
(Reuters) - Real Madrid, Manchester United and Paris St Germain reached the last 16 of the Champions League on Wednesday on a night when the goals flowed all over Europe with United the highest scorers in a 5-0 win at Bayer Leverkusen.
News of all that's transpired on and off the football field
A summary of Wednesday night's matches inthe UEFA Champions League.
News of all that's transpired on and off the football field
A summary of all the Champions League matches played across Europe on Tuesday
News of all that's transpired on and off the football field
Photos from the Champions League matches played across Europe on Tuesday.
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