[3] Though he never secured himself in the Frem starting line-up,[3] Bille played a total 38 senior games and scored four goals for the club until August 2006.

In September 2006, he moved abroad to play for Italian club Reggina Calcio in the Serie A championship,[4] under manager Walter Mazzarri.

[6] Under new manager Massimo Ficcadenti, Bille had a difficult time securing a place in the starting eleven,[7] and he underwent loan deals with Serie C1 teams A.C. Martina and A.S. Lucchese-Libertas.

[8] He brought with him an eight match-day suspension incurred following a red card for laying his hand on the referee in a May 2008 youth team game for Lucchese.

[16] Nicki Bille gained his first team debut 5 February 2011 in a home fixture against Levante FC, Villarreal CF lost the game 0–1.

On 3 January 2013 he signed a four-year deal with Norwegian side Rosenborg after ending his stay at Rayo Vallecano earlier than planned.

officially announced the purchase of experienced Danish international striker Nicki Niels Bille Nielsen from Lech Poznań, for an undisclosed fee.

He was called up for the Danish under-20 national team for the 2006 Milk Cup in August, as a replacement for the injured Nicklas Pedersen,[26] and scored one goal in two games at the tournament.

After his loan to Martina, he was called up for the Denmark national under-21 football team to replace the injured Bo Storm,[27] and made his under-21 debut in September 2007.

On 22 October 2018, he was arrested on Strøget in Central Copenhagen and charged with making threats of violence including threatening to fire his airgun at another individual.

This led to him being sacked by Lyngby Boldklub[33] who had publicly stated that they gave the striker a chance to redeem his career and get his life back on track, when they offered him a contract.

On 25 December 2018, Nielsen was seriously injured in the right arm, when three people entered his flat in the Sydhavnen District of Copenhagen and shot him with a shotgun.