Nick Levin of Digital Spy gave the song a positive review stating:
This breakthrough smash is indeed an almighty racket. But it is the very best kind of almighty racket, a swaggering synthesis of beats, power chords, stadium keyboard hooks, crowd noise and vocals from the lungularly-blessed Alana that sounds like the sort of thing David Haye might hear in his head as he struts into the ring. Memo to Emily Eavis: book this lot for Glasto now… but remember to buy the poor cows some ear muffs first! .
"Me and You" debuted on the UK Singles Chart on 9 January 2011 at number 15; marking that week's highest new entry. The single also debuted at the number-one spot on the independent releases chart, knocking Adele's "Make You Feel My Love" from her eight-week reign. The following week, the single remained at number 15; although losing its number-one place on the independent releases chart to Adele; who once again returned to the peak. The single also qualified for the dance chart on 16 January 2011; debuting at number 3. On 23 January 2011, the single fell 7 places to number 22 and fell a further 4 places to number 26 the following week; marking its fourth week within the top 40.
A music video to accompany the release of "Me and You" was first posted onto YouTube on 5 December 2010. The video begins with a teenage boy entering a video game arcade and playing a driving game, followed by a shooting game. During his game, Nero walk past before exiting out a back door; grabbing the boy's curiosity. The boy follows, leading him down a deserted corridor; where he finds a room. Entering the room, the boy discovers an arcade game entitled 'Nero' and after following the instructions to insert credit; begins his game playing as Joe to the backing track "Me and You". The game, very much similar to Streets of Rage 3 & Outrun 2019, shuts down during the boy's playing, who after searching, discovers the plug has been removed and places it back in. Continuing the game, the boy comes to a conclusion when the characters Joe and Dan come across a young boy playing an arcade game. As of March 2013, the music video has received over 8 million views.