In January 2010, Ne-Yo was featured in a duet with singer Mariah Carey titled "Angels Cry".
In June 2010, Ne-Yo released the single "Beautiful Monster", which became Ne-Yo's first number-one single on the UK Singles Chart. It peaked at number 53 on the Billboard Hot 100 chart.
On October 8, 2010, Ne-Yo performed some of his songs from the new album at P.C. Richard & Son Theater in New York City, an event hosted by iHeartRadio. Ne-Yo made an appearance at New York ComicCon to announce that he was collaborating with Stan Lee for a Libra Scale comic. Ne-Yo also met with fans for pictures and autographs in the Cultyard of the ComicCon. The second and third singles released from the album are "Champagne Life" and "One in a Million", respectively.
Libra Scale was released on November 22, 2010. It received critical acclaim from music critics, but was a commercial disappointment, debuting at number nine on the US Billboard 200 chart, selling less than all of his previous three studio albums. Ne-Yo stated: "The album is based upon this short story which basically follows these three characters who are forced to choose between money-power-and-fame versus love. Which in turn is why I've called it 'Libra Scale'. You know, its whole concept is based on that question of morality – that, if you weighed it all out on a libra scale, which one of those two options would you choose?". Libra Scale sold 112,000 copies in its first week. In the United Kingdom, the album debuted at number 11 on the UK Albums Chart, while debuting at number one on the UK R&B Chart.
In 2010, he dueted with Mariah Carey on "Angel's Cry", a song for her cancelled album, Angels Advocate. Ne-Yo has also written songs for Celine Dion, Whitney Houston, Carrie Underwood, Anastacia, Ciara, Corbin Bleu, Enrique Iglesias, and Dima Bilan. He collaborated with Lindsay Lohan on her new material, having already finished "Bossy", a pre-single for her new album Spirit in the Dark. In 2007, Ne-Yo confirmed that he had been contacted by producer will.i.am to work on what would have been Michael Jackson's new album. However, at the time of Jackson's death, Ne-Yo's collaborations with him had yet to move past the writing stage. In an interview in 2010, Ne-Yo said that, since Jackson's death, he had been confused as what to do with the songs, as he felt that selling them to another artist or even releasing the songs himself would be disrespectful to Jackson's legacy. In 2009, he wrote "Truth (Saigo no Shinjitsu)" for w-inds., the Japanese pop group.
In June 2010, Ne-Yo told Ebony that he and his then-girlfriend, Monyetta Shaw, were expecting their first child together – a girl due early in 2011. Shaw gave birth early to daughter Madilyn Grace Smith on November 12, 2010, in Atlanta, Georgia. Announcing the birth, Ne-Yo said of his first child, "I've been in love before but this feels like nothing I've ever felt... like I'm in love for the first time."