Little is a graduate of Cullman High School. He attended UAB, completing his bachelor of arts in 1991, and earned his juris doctorate at Samford University's Cumberland School of Law in 1994. He is a member of the Alabama State Bar, the Cullman County Bar Association and the Bar Associations of the U. S. District Court for the Northern and Middle Districts of Alabama.
Little was first elected to the Senate in 2002, defeating former Republican Governor Guy Hunt for the seat representing Senate District 4 (Cullman, Lawrence and Winston Counties). He was appointed Senate Floor Leader by the President Pro Tempore of the Senate in 2002.
Little was re-elected to the Senate in 2006 and kept his position as Floor Leader. Halfway through his second term, he was elected as Senate Majority Leader to fill a vacancy. As such he served on all Senate standing committees, except those pertaining to local legislation outside of his district. He did chair the Committee on Local Legislation No. 1. He was again elected by his fellow Senators as Senate Majority Leader for the Term 2007–2010.
On April 3, 2009 Little was arrested by Alabama State Troopers for driving under the influence of alcohol, driving with an open container, driving with an expired license, and failure to yield to an emergency vehicle after a witness reported his 2008 GMC Sierra leaving the scene of an accident on I-65 North near Vestavia Hills.
Little subsequently resigned his position as prosecutor for the city of Hanceville. He pleaded guilty and was given a fine, a 30-day suspended sentence, and a 1 year probation. He was not re-elected in the 2010 general election and currently practices law in Cullman as a partner in Griffith, Little & Lowry. In 2019 Little was charged with three counts of first-degree theft for allegedly stealing more than $25,000 from client trust funds. He pleaded guilty in September before specially-appointed Judge Terry Dempsey.
Little is married to the former Deanna Smith of Cullman and has two children, Zeb, Jr and Emily. The family attends St John's Evangelical Protestant Church in Cullman.
- Taylor, Kelli Hewett (April 4, 2009) "State Sen. Zeb Little, Alabama senate majority leader, arrested for DUI." The Birmingham News
- Velasco, Eric (May 18, 2009) "Alabama state Sen. Zeb Little of Cullman pleads guilty to DUI." The Birmingham News
- Speakman, Jamie (February 21, 2019) "Former State Senator Zeb Little Arrested." Cullman Today
- Remkus, Ashley (September 24, 2019) "Former Alabama senator Zeb Little pleads guilty to stealing from legal clients." The Birmingham News