As a receiver for the University of Toledo, Moore compiled 2,776 yards and 25 touchdowns on 222 receptions in 50 career games from 2001 to 2004. He also had 902 kick return yards and 399 punt return yards with two punt returns for touchdown. In the 2004 Mid-American Conference championship, he caught three of Bruce Gradkowski's four touchdown throws in a victory against Miami University. Moore was also the only person in Toledo school history to gain over 1,000 yards twice and set a school single season mark with 14 touchdown receptions as a senior. Moore was twice elected as a first-team All-Mid American Conference player. Moore majored in business at Toledo.
Lance Moore was signed as an undrafted free agent by the Cleveland Browns on April 29, 2005. He was later released and then signed to the New Orleans Saints' practice squad.
2006
Moore was allocated by the New Orleans Saints to NFL Europe, where he played for the Berlin Thunder. He was on the Saints active roster for 6 games and saw action in four of those games with roles as a returner and wide receiver. He was waived by the team on October 29 and then re-signed to the practice squad the following day.
On October 14, 2007, he got the first opportunity of his professional career to start. He started alongside wide receiver Marques Colston and scored the first touchdown of his career on a 7-yard end around against the Seattle Seahawks with 05:18 remaining in the second quarter.
Moore started the 2008 season as the Saints number three wide receiver. When number one wide receiver Marques Colston was sidelined with a broken finger, Moore was given more playing opportunity and made his way up to the number two position. The 2008 NFL season proved to be the best yet for Lance Moore as he made the most of his playing time by starting for an injured Marques Colston and ended the season with 79 receptions, for 928 yards and adding 10 touchdowns.
Due to an ankle and hamstring injuries, Moore's numbers throughout most of the season have been down from his 2008 breakout season. However, when healthy, he was able to achieve a 6 catch, 78 yard performance in the postseason. Against the Colts in Super Bowl XLIV, he had two receptions for 21 yards in the first half, and a 4th quarter catch for a two-point conversion.
2010–2013
Due to Reggie Bush being sidelined with an injury, Moore had a breakout performance against the Atlanta Falcons in 2010. Moore ended the season with 66 catches for 763 yards and eight touchdowns. In 2011, Moore recorded 627 yards and eight touchdowns. In 2012, Moore had the best season of his career with 1,041 yards and six touchdowns. He finished second on the team in receiving yards. Moore's role diminished in 2013 as he struggled with injuries, missing three games and recording only 457 yards and two touchdowns. He became the team's fourth receiving option on the depth chart behind emerging rookie Kenny Stills. On March 7, 2014, Moore was released by the Saints.
Pittsburgh Steelers
2014
On March 21, 2014, Moore signed a two-year deal with the Pittsburgh Steelers. He was released on March 2, 2015.
Detroit Lions
2015
On May 12, 2015, Moore signed a one-year contract with the Detroit Lions. On November 26, during a game against the Philadelphia Eagles, Moore left with an ankle injury. Moore was later ruled out for Thursday's Week 13 game. Moore finished the season with 29 catches for 337 yards and four touchdowns.
Atlanta Falcons and retirement
2016 season
On August 5, 2016, Moore signed with the Atlanta Falcons. Three days later, the team announced that Moore had decided to retire from the NFL. On May 30, 2017, Moore signed a one-day contract to retire as a New Orleans Saint.