Prior to joining Bloomberg, Ruhle spent 14 years working in the Finance industry. While in college, she spent a summer interning for Merrill Lynch. In 1997, she joined Credit Suisse where she spent six years working in hedge fund sales. During her time at Credit Suisse First Boston, she served as a vice President and became the highest producing credit derivatives salesperson in the United States. In 2003, Ruhle joined Deutsche Bank as a credit salesperson covering hedge funds. She ended her eight-year career there as a managing Director in Global Markets Senior Relationship Management. While at Deutsche Bank, Ruhle founded the Global Market Women's Network to help women move into leadership roles at the company.

Ruhle joined Bloomberg Television in October 2011, where she co-hosted a two-hour early morning program called Inside Track with co-anchor Erik Schatzker. In 2012, Ruhle and Schatzker joined Market Makers, a two-hour late morning program. Ruhle then co-hosted Bloomberg GO with David Westin before leaving the network. She has profiled figures including former New York City Mayor Michael Bloomberg, Goldman Sachs CEO Lloyd Blankfein, hedge fund managers Stanley Druckenmiller and David Tepper, NBA player Kobe Bryant, Donald Trump, chairman and CEO of JP Morgan Jamie Dimon, Martha Stewart, Sean Parker, former Vice President Al Gore, Business magnate Russell Simmons, Masters winner Jordan Spieth, Miami Heat star Dwyane Wade, CEO and chair of Macy's Terry Lundgren, and music moguls Sean Combs and Kanye West.

Ruhle is a columnist for Shape.com, the website for Shape magazine. Ruhle was featured on the cover of Working Mother magazine in October 2012, as well as Fit Pregnancy on their April/May 2013 issue. She has been profiled by 201 Magazine, Glass Hammer, IWantHerJob, and Business Insider. No longer with Bloomberg, Ruhle is now part of the MSNBC Morning Lineup, and, with Ali Velshi, co-hosts a weekly Saturday Business program, Velshi & Ruhle.

In June 2013, Ruhle wrote a provocative response to Paul Tudor Jones’ comments on women in trading for the Huffington Post that elicited responses from both the media and financial industries. In October of that same year, Ruhle sat down with Martha Stewart to discuss social media, blogging, and the creation of the "lifestyle" category.

She interviewed in 2015 then-presidential candidate Donald Trump, who faced backlash in the media after noting to Ruhle that "the World Trade Center came down during [former President George W. Bush’s] reign." The previous year, Rapper Kanye West strongly criticized Photographer Annie Leibovitz during a panel conversation with Ruhle when he revealed that Leibovitz pulled out of taking his official wedding pictures just one day before his wedding to Kim Kardashian. Ruhle’s interview with Martha Stewart in 2013 brought an ongoing feud between Stewart and Gwyneth Paltrow public after Stewart questioned the actress’s place in the "lifestyle business".

She is a graduate of Lehigh University where she earned her bachelor’s degree in international Business in 1997. As part of her major, she studied in Guatemala, Italy, and Kenya. Ruhle returned to Lehigh to give the 2017 commencement address.