Rancic is of Croatian and Irish extraction. He was born in Chicago, Illinois and grew up in the suburb of Orland Park. He attended St. Michael's School in Orland Park, and graduated from Carl Sandburg High School.

Rancic attended Bradley University in Peoria, Illinois for his freshman year of college, majoring in Criminal Justice with a focus on going to law school. During this time Rancic's father took a teaching job at Loyola University Chicago, allowing Rancic the free tuition benefit enjoyed by all dependents of faculty members. He eventually received a Bachelor of Science degree from Loyola University, graduating cum laude in 1994. He never attended law school.

During his college years Rancic worked at FAO Schwarz as a security guard. Next he took up a boat detailing business on the side prior to starting his online cigar business, which helped him negotiate the price of a cigar during one of Trump's tasks of negotiation.

Rancic was one of the job applicants in The Apprentice 1 during the spring of 2004, as one of 16 contestants. Rancic was hired at the conclusion of the 14-week job interview after Donald Trump fired Kwame Jackson.

Rancic was the first reality TV star to be hired on national television, and with an audience over 28 million viewers, had to decide in three minutes which Trump project to manage. Rancic elected to take charge of the construction of the Trump Tower Chicago in his native Chicago, Illinois, on the site of the demolished Chicago Sun-Times building. His other option was to oversee and manage a new Trump National Golf Course and resort in Los Angeles, California. The Trump National course was a potential site for season 6 of the show.

Most of Trump's advisors thought Bill was the one during the episode "Down to the Wire". In this episode, he explained that things not being to his satisfaction is sometimes a blessing but also a curse.

For the final challenge against competitor Kwame Jackson, Trump gave Rancic the task of running a celebrity golf outing at Briarcliff Manors, while Jackson was tasked to manage a Jessica Simpson concert. At the final board meeting, Jackson remarked that running a golf outing was the easier of the two tasks, which brought a disagreement from Trump VP Carolyn Kepcher, who was managing a golf course when Trump hired her. Trump hired Rancic for doing a very good job.

As an Apprentice judge

Originally Rancic said that after his one-year contract as being Donald Trump's Apprentice expired, he would leave the job and start his own company . He instead opted to remain part of the Trump Organization, and in some seasons filled in as a judge when regular judge George Ross was away on business.

Work outside of Trump

In September 2007, Rancic co-hosted iVillage's In the Loop with iVillage a TV show and webcast produced by NBC Universal. NBC commissioned a set at the Universal Orlando Resort in Florida. In September 2008, Rancic began as host for the A&E reality show, We Mean Business, in which small business owners undergo business make-overs.

In 2008, Rancic and his wife, TV host Giuliana Rancic (née DePandi) started a joint television production company, You and I Productions, which produces reality and scripted programming for television.

On December 15, 2006, he became engaged to E! News co-host Giuliana DePandi . They were married on September 1, 2007, on the island of Capri, Italy. Bill and his wife Guiliana suffered a miscarriage in 2010.

Rancic splits his time between Hinsdale, Illinois and Los Angeles, California.