De Gea made his first appearance for Manchester United in a 3–1 friendly win over Chicago Fire on 23 July 2011. He made his competitive debut for United against Manchester City in the Community Shield on 7 August. Despite being caught out in the first-half by a header from Joleon Lescott and a long-range Edin Džeko strike that put City into a 2–0 lead, United rallied in the second half and won 3–2. De Gea made his league debut for Manchester United against West Bromwich Albion a week later, where he received criticism for failing to save Shane Long's goal during a 2–1 United victory, which Ferguson described as "a learning process". De Gea kept his first clean sheet for United on his Old Trafford debut in the following fixture, a 3–0 victory against Tottenham Hotspur. In the following match, six days later, De Gea saved a penalty from Arsenal captain Robin van Persie, which would have cancelled out United's 1–0 lead. He made further saves to deny Van Persie and Andrey Arshavin in United's 8–2 victory. Teammate Wayne Rooney backed De Gea to succeed at United and hailed him as a "strong character".
On 18 September, Manchester United beat Chelsea 3–1 at Old Trafford, with De Gea making a string of impressive saves, particularly from Ramires – when the midfielder had an empty net to side-foot home, De Gea quickly got across to smother the ball away. De Gea's improvement in form continued in his next appearance, as he made two stunning saves to help his team to a 1–1 draw away at Stoke City, and his overall performance was praised by teammates Patrice Evra and Darren Fletcher. De Gea made his first ever UEFA Champions League start in a 3–3 draw against Basel on 27 September 2011. On 15 October, De Gea was praised for his efforts at Anfield as United drew 1–1 against Liverpool, providing important saves in a nerve-free performance, prompting Liverpool manager Kenny Dalglish to joke, "I thought the press said the boy was struggling."
On 23 October 2011, De Gea played as Manchester United suffered their worst home defeat since 1955 with a 6–1 loss against cross-town rivals Manchester City, the first time United had conceded six goals at home since 1930. De Gea was in goal during the league defeat to Blackburn Rovers and was blamed by most media outlets for failing to deal with an aerial ball that led to the conceding of a late goal by Grant Hanley in a 3–2 defeat. De Gea was nonplussed by the error, saying, "all keepers make mistakes once in a while and none of us like it when we do. I have every intention of spending many years here at Manchester United. I want to become a great United keeper and I want to earn and deserve the respect I hope to get," and spoke of his intentions of surpassing his predecessor: "Hopefully, I will equal or even surpass the performance and contribution Edwin van der Sar made to the club." After this match, De Gea was dropped and replaced by United's second-choice goalkeeper, Anders Lindegaard. An injury to Lindegaard saw De Gea return to the starting line-up for a 3–3 draw with Chelsea at Stamford Bridge on 5 February 2012. De Gea later cited his last-minute save from Juan Mata during this match as the turning point in his season, as he went on to play the club's last 19 matches, keeping eight clean sheets.
Under new Manchester United manager José Mourinho, De Gea made his first appearance of the season in the FA Community Shield against Premier League winners Leicester City. The match ended in a 2–1 victory for United. De Gea started the Premier League season by keeping 2 clean sheets in his first 3 games against Southampton and Hull City. De Gea was part of the Manchester United team which lost 4–0 to Chelsea, their heaviest Premier League defeat since the 6–1 loss against Manchester City in October 2011.
De Gea helped Spain's under-17 team win the 2007 European Championship, and finish second at the 2007 World Cup. In early May 2010, courtesy of solid Atlético performances, he was named by senior squad manager Vicente del Bosque in a provisional 30-man squad for the 2010 FIFA World Cup; however, he did not make the final cut. In 2011, he was part of the Spain under-21 team that won the 2011 UEFA European Under-21 Championship.